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Ryuichi Tatsumi Last modified date:2018.06.21

Associate Professor / Animal & Mairne Bioresource Sciences
Department of Bioresource Sciences
Faculty of Agriculture


Graduate School
Undergraduate School


E-Mail
Homepage
http://www.agr.kyushu-u.ac.jp/biosci-biotech/chikusan/
Brief sketch of research faculty, projects and activities .
Phone
092-642-2950
Fax
092-642-2951
Academic Degree
Ph.D.
Field of Specialization
Muscle Cell Biology, Muscle and Meat Biochemistry, Mechanobiology
Outline Activities
Outline of research:
1) Molecular mechanism of meat tenderlization during postmortem aging of meat.
Giant myofibrillar proteins connectin (also called titin, 3000 kDa) and nebulin (800 kDa) have been shown to split into subfragments through the binding of calcium ions to their filamentous molecules, beeing responsible for meat tenderlization during postmortem aging.

2) Gene expression analysis of giant myofibrillar proteins during neonatal myogenesis.
Giant myofibrillar proteins connectin and nebulin were evaluated for their gene expression during neonatal myogenesis. In this precess, we have found a new lipoprotein having a chain weight of 500 kDa, and reported its characterization and localization in skeletal muscle tissue.

3) Molecular mechanism of postnatal muscle growth and regeneration.
Satellite cells, resident myogenic stem cells found between the basement membrane and the sarcolemma, are normally quiescent most of the time in adult skeketal muscle. When muscle is injured, overused or mechanically stretched, these cells are activated to enter the cell cycle, divide, differentiate and fuse with muscle fibers to repair damaged regions and to enhance hypertrophy of muscle fibers. We have shown that hepatocyte growth factor (HGF) is present in extracellular matrix of uninjured adult muscle and that HGF can activate quiescent satellite cells through its rapid release from the extracellular association and its subsequent presentation to the c-met receptor (Tatsumi et al. 1998, Dev. Biol.; 2001, Exp. Cell Res). HGF release was dependent on calcium-calmodulin formation and nitric oxide (NO) production by NO syntase in response to mechanical perturbation of muscle (Tatsumi et al. 2002, Mol. Biol. Cell) . According to these findinds, we have proposed a activation cascade to translate mechanical changes in muscle tissue into chemical signals that can activate satellite cells.

Education:
Seminars and lectures in Bioscience and Biotechnology at undergraduate and graduate levels.

Others:
a member of Kyushu University Research Core "Food Safety and Healthy Life (Research Head: Prof. Imaizumi, K.)" (Oct. 2004-).
Research
Research Interests
  • Molecular mechanisms for satellite cell activation entry into the cell cycle
    keyword : muscle hypertrophy, regeneration, HGF, satellite cells, activation, NO radical, NOS, calmodulin, calcium ions, proteoglycan, MMP, myofiber, skeletal muscle
    1996.02Research Title: Molecular Mechanism of Mechanical Perturbation-induced Activation of Skeletal Muscle Satellite Cells..
  • Molecular mechanisms for satellite cell quiescence
    keyword : muscle hypertrophy, regeneration, satellite cells, activation, quiescence, myostatin (GDF8), proteoglycan, myofiber, skeletal muscle, meat
    2003.09Research Title: Molecular Mechanism of Muscle Satellite Cell Quiescence and its application to Skeletal Muscle Hypertrophy and Regeneration..
  • Possible Changes in Muscle Fiber Types by Functional Food Ingredients.
    keyword : fiber types, satellite cells, myotubes, beef extract, polyphenol
    2005.04Research Title: Possible Changes in Muscle Fiber Types by Functional Food Ingredients..
  • New role of muscle satellite cells: implication in regenerative motoneuritogenesis
    keyword : muscle hypertrophy, regeneration, satellite cells, neurochemorepellent, myofiber, skeletal muscle, ALS
    2007.04Research Title: Molecular Mechanism of Motor Neuron Network Formation in Skeletal Muscle..
Current and Past Project
  • Research Title: Possible Local Communocation between Myogenic Stem Cells and Motoneuron Terminals.
    Abstract: Regenerative coordination and remodeling of the intramuscular motoneuron network and neuromuscular connections are critical for restoring skeletal muscle function and physiological properties. The regulatory mechanisms of such coordination remain unclear, although both attractive and repulsive axon guidance molecules may be involved in the signaling pathway. Recent our studies highlight a heretofore unexplored and active role for satellite cells as a key source of neural secreted chemorepellent Sema3A expression triggered by HGF, hence suggesting that regenerative activity toward motor innervation may importantly reside in satellite cells and could be a crucial contributor during postnatal myogenesis (Tatsumi et al. 2009, American Journal of Physiology-Cell Physiology 297, C238-C252, selected for the Editorial Focus.)
  • Research Title: Molecular Mechanism of Muscle Satellite Cell Quiescence.
    Abstract: Skeletal muscle regeneration and work-induced hypertrophy rely on molecular events responsible for activation and quiescence of resident myogenic stem cells, satellite cells. Recent studies demonstrated that hepatocyte growth factor (HGF) triggers activation and entry into the cell cycle in response to mechanical perturbation, and that subsequent expression of myostatin may signal a return to cell quiescence. However, mechanisms responsible for coordinating expression of myostatin after an appropriate time-lag following activation and proliferation are not clear. Our recent publications demonstrated that HGF could induce satellite cell quiescence by stimulating myostatin expression. The HGF concentration required (over 10-50 ng/ml), however, is much higher than that for activation. Considering that HGF is produced by satellite cells and spleen and liver cells in response to muscle damage, local concentrations of HGF bathing satellite cells may reach a threshold sufficient to induce myostatin expression. This time-lag may delay action of the quiescence signaling program in proliferating satellite cells during initial phases of muscle regeneration followed by induction of quiescence in a subset of cells during later phases (Yamada et al. 2010. American Journal of Physiology-Cell Physiology 298, C465–C476, selected for the Editorial Focus).
  • Research Title: Molecular Mechanism of Mechanical Perturbation-Induced Activation of Muscle Satellite Cells.
    Abstract: In undamaged postnatal muscle fibers with normal contraction and relaxation activities, quiescent satellite cells of resident myogenic stem cells are interposed between the overlying external lamina and the sarcolemma of a subjacent mature muscle fiber. When muscle is injured, exercised, overused or mechanically stretched, these cells are activated to enter the cell proliferation cycle, divide, differentiate, and fuse with the adjacent muscle fiber, and are responsible for regeneration and work-induced hypertrophy of muscle fibers. Therefore, a mechanism must exist to translate mechanical changes in muscle tissue into chemical signals that can activate satellite cells. Recent studies of satellite cells or single muscle fibers in culture and in vivo demonstrated the essential role of hepatocyte growth factor (HGF) and nitric oxide (NO) radical in the activation pathway. These experiments have also reported that mechanically stretching satellite cells or living skeletal muscles triggers the activation by rapid release of HGF from its extracellular tethering and the subsequent presentation to the receptor c-met. HGF release has been shown to rely on calcium-calmodulin formation and NO radical production in satellite cells and/or muscle fibers in response to the mechanical perturbation, and depend on the subsequent up-regulation of matrix metalloproteinase (MMP) activity. These results indicate that the activation mechanism is a cascade of events including calcium ion influx, calcium-calmodulin formation, NO synthase activation, NO radical production, MMP activation, HGF release and binding to c-met. Better understanding of ‘mechano-biology’ on the satellite cell activation is essential for designing procedures that could enhance muscle growth and repair activities in meat-animal agriculture and also in neuromuscular disease and aging of human (Tatsumi & Allen 2008, Animal Science Journal 79, 279-290, invited review; Tasumi 2010, Animal Science Journal 81, 11-20, invited review).
Academic Activities
Reports
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5. Tatsumi, R. (2007) Improvement of Age-Related Sarcopenia by Functional Food Ingredients., The Research Reports of the Uehara Memorial Foundation, 21, 92-94..
6. Tatsumi, R. and Ikeuchi, Y. (2005) More shine to Meat Production: a Programmed Cascade for Muscle Satellite Cell Activation and Quiescence. Proceedings of Japanese Society for Animal Nutrition and Metabolism, 49(1), 1-19..
7. Tatsumi, R. (2001) Molecular Mechanism of Muscle Satellite Cell Activation., Shokuniku-no-Kagaku 42 (2), 123-133..
8. Tatsumi, R. (1997) Activation of Muscle Stem Cells, Kagaku-to-Seibutsu 35(4), 295-297..
Papers
1. Judy E. Anderson, Mai-Khoi Q. Do, N. Daneshvar, Takahiro SUZUKI, J. Dort, Wataru Mizunoya, Ryuichi Tatsumi, The role of semaphorin 3A in myogenic regeneration and the formation of functional neuromuscular junctions on new fibers, Biological Reviews, 10.1111/brv.12286, 10.1111/brv.12286, 2017.08.
2. Tatsumi, Ryuichi; Suzuki, Takahiro; Do, Mai-Khoi Q.; Ohya, Yuki; Anderson, Judy E.; Shibata, Ayumi; Kawaguchi, Mai; Ohya, Shunpei; Ohtsubo, Hideaki; Mizunoya, Wataru; Sawano, Shoko; Komiya, Yusuke; Ichitsubo, Riho; Ojima, Koichi; Nishimatsu, Shin-ichiro; Nohno, Tsutomu; Ohsawa, Yutaka; Sunada, Yoshihide; Nakamura, Mako; Furuse, Mitsuhiro; Ikeuchi, Yoshihide; Nishimura, Takanori; Yagi, Takeshi; Allen, Ronald E., Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells, STEM CELLS, 10.1002/stem.2639, 35, 7, 1815-1834, 2017.07.
3. Wataru Mizunoya, Shinpei Okamoto, Hideo Miyahara, Mariko Akahoshi, Takahiro SUZUKI, Mai-Khoi Q. Do, Hideaki Ohtsubo, Yusuke Komiya, Mulan Qahar, Toshiaki Waga, Koichi Nakazato, Yoshihide Ikeuchi, Judy E. Anderson, Ryuichi Tatsumi, Fast-to-slow shift of muscle fiber-type composition by dietary apple polyphenols in rats: Impact of the low-dose supplementation, Animal Science Journal, 10.1111/asj.12655, 88, 3, 489-499, 10.1111/asj.12655, 2017.04, Our previous studies demonstrated that an 8-week intake of 5% (w/w) apple polyphenol (APP) in the diet improves muscle endurance of young-adult rats. In order to identify a lower limit of the dietary contribution of APP to the effect, the experiments were designed for lower-dose supplementation (8-week feeding of 0.5% APP in AIN-93G diet) to 12-week-old male Sprague-Dawley rats. Results clearly showed that the 0.5% APP diet significantly up-regulates slower myosin-heavy-chain (MyHC) isoform ratios (IIx and IIa relative to total MyHC) and myoglobin expression in lower hind-limb muscles examined (P < 0.05). There was a trend to increased fatigue resistance detected from measurements of relative isometric planter-flexion force torque generated by a stimulus train delivered to the tibial nerve (F (98, 1372) = 1.246, P = 0.0574). Importantly, there was no significant difference in the animal body-phenotypes or locomotor activity shown as total moving distance in light and dark periods. Therefore, the present study encourages the notion that even low APP-intake may increase the proportions of fatigue-resistant myofibers, and has promise as a strategy for modifying performance in human sports and improving function in age-related muscle atrophy..
4. Hideaki Ohtsubo, Yusuke Sato, Takahiro SUZUKI, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi, Data supporting possible implication of APOBEC2 in self-renewal functions of myogenic stem satellite cells: toward understanding the negative regulation of myoblast differentiation, Data in Brief, 10.1016/j.dib.2017.03.051, 10.1016/j.dib.2017.03.051, 2017.04, This article provides in vitro phenotypical data to show that APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, may implicate in self-renewal functions of myogenic stem satellite cells, namely in the re-establishment of quiescent status after activation and proliferation of myoblasts in single-myofiber culture..
5. Hideaki Ohtsubo, Yusuke Sato, Takahiro SUZUKI, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi, APOBEC2 negatively regulates myoblast differentiation in muscle regeneration, International Journal of Biochemistry and Cell Biology , 10.1016/j.biocel.2017.02.005, 85, 91-101, 10.1016/j.biocel.2017.02.005, 2017.03, Recently we found that the deficiency of APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, leads to a diminished muscle mass and increased myofiber with centrally-located nuclei known as dystrophic phenotypes. APOBEC2 expression is predominant in skeletal and cardiac muscles and elevated exclusively at the early-differentiation phase of wild-type (WT) myoblast cultures; however the physiological significance is still un-known. Here we show that APOBEC2 is a key negative regulator of myoblast differentiation in muscle regeneration. APOBEC2-knockout (A2KO) mice myoblast cultures displayed a normal morphology of primary myotubes along with earlier increase in fusion index and higher expression levels of myosin heavy chain (MyHC), myogenin and its cooperating factor MEF2C than WT myoblasts. Similar response was observable in APOBEC2-knockdown cultures of WT myoblasts that were transfected with the specific siRNA at the differentiation phase (not proliferation phase). Importantly, cardiotoxin-injured A2KO gastrocnemius muscle provided in vivo evidence by showing larger up-regulation of neonatal MyHC and myogenin and hence earlier regeneration of myofiber structures with diminished cross-sectional areas and minimal Feret diameters. Therefore, the findings highlight a promising role for APOBEC2 in normal progression of regenerative myogenesis at the early-differentiation phase upon muscle injury..
6. Mai-Khoi Q. Do, Naomi Shimizu, Takahiro Suzuki, Hideaki Ohtsubo, Wataru Mizunoya, Mako Nakamura, Shoko Sawano, Mitsuhiro Furuse, Yoshihide Ikeuchi, Judy E. Anderson, Ryuichi Tatsumi, Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts, Physiological Reports, 10.14814/phy2.12553, 3, 9, e12553, 2015.09, Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early-differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin-sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two-magnitude higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knock-down diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pre-treatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively in non-knock-down cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle-fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery..
7. Wataru Mizunoya, Hideo Miyahara, Shinpei Okamoto, Mariko Akahoshi, Takahiro Suzuki, Mai-Khoi Q. Do, Hideaki Ohtsubo, Yusuke Komiya, Mu Lan, Toshiaki Waga, Akira Iwata, Koichi Nakazato, Yoshihide Ikeuchi, Judy E. Anderson, Ryuichi Tatsumi, Improvement of endurance based on muscle fiber-type composition by treatment with dietary apple polyphenols in rats, PLoS ONE, 10.1371/journal.pone.0134303, 10, 7, e0134303, 2015.07, A recent study demonstrated a positive effect of apple polyphenol (APP) intake on muscle endurance of young-adult animals. While an enhancement of lipid metabolism may be responsible, in part, for the improvement, the contributing mechanisms still need clarification. Here we show that an 8-week intake of 5% (w/w) APP in the diet, up-regulates two features related to fiber type: the ratio of myosin heavy chain (MyHC) type IIx/IIb and myoglobin protein expression in plantaris muscle of 9-week-old male Fischer F344 rats compared to pair-fed controls (P < 0.05). Results were demonstrated by our SDS-PAGE system specialized for MyHC isoform separation and western blotting of whole muscles. Animal-growth profiles (food intake, body-weight gain, and internal-organ weights) did not differ between the control and 5% APP-fed animals (n = 9/group). Findings may account for the increase in fatigue resistance of lower hind limb muscles, as evidenced by a slower decline in the maximum isometric planter-flexion torque generated by a 100-s train of electrical stimulation of the tibial nerve. Additionally, the fatigue resistance was lower after 8 weeks of a 0.5% APP diet than after 5% APP, supporting an APP-dose dependency of the shift in fiber-type composition. Therefore, the present study highlights a promising contribution of dietary APP intake to increasing endurance based on fiber-type composition in rat muscle. Results may help in developing a novel strategy for application in animal sciences, and human sports and age-related health sciences..
8. Shoko Sawano, Takahiro Suzuki, Mai-Khoi Q. Do, Hideaki Ohtsubo, Wataru Mizunoya, Yoshihide Ikeuchi, Ryuichi Tatsumi, Supplementary immunocytochemistry of hepatocyte growth factor production in activated macrophages early in muscle regeneration, Animal Science Journal, 10.1111/asj.12264, 85, 12, 994-1000, 2014.12, Regenerative intramuscular motor-innervation is thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies showed that resident myogenic stem cells, satellite cells, up-regulate a secreted neural-chemorepellent semaphorin 3A (Sema3A) during the early-differentiation period, in response to hepatocyte growth factor (HGF) elevated in injured muscle. However, a paracrine source of the HGF release is still unknown. Very recently, we proposed a possible contribution of anti-inflammatory macrophages (CD206-positive M2) by showing that M2 cells infiltrate predominantly at the early-differentiation phase (3-5 days post-injury) and produce/secrete large amounts of HGF. In understanding this concept, however, there still remains a critical need to examine if phagocytotic pro-inflammatory macrophages (CD86-positive M1), another activated-phenotype still present at the early-differentiation phase concerned, produce HGF upon muscle injury. The current immunocytochemical study demonstrated that the HGF expression is negative for M1 prepared from cardiotoxin-injured tibialis anterior muscle at day-5, in contrast to the intense fluorescent-signal of M2 served as a positive control. This supplementary result advances our understanding of a spatiotemporal burst of HGF secretion from M2 populations (not M1) to impact Sema3A expression, which ensures a coordinated delay in attachment of motoneuron terminals onto damaged and generating fibers during early phase of muscle regeneration..
9. Shohei Sakaguchi, Jun-ichi Shono, Takahiro Suzuki, Shoko Sawano, Judy E. Anderson, Mai-Khoi Q. Do, Hideaki Ohtsubo, Wataru Mizunoya, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Ryuichi Tatsumi, Anti-inflammatory macrophages implicate in regenerative moto-neuritogenesis, by promoting myoblast migration and Sema3A expression, Animal Science Congress 2014 of the Asian-Australian Association of Animal Production Societies (AAAP) Grha Sabha Pramana, Universitas Gadjah Mada (UGM), Yogyakarta, Indonesia (November 10-14, 2014), 2014.11, Successful regeneration and remodeling of neuromuscular connections are critical for restoring functional properties of muscle fiber contractility. While the spatiotemporal regulatory mechanisms coordinating these processes (moto-neuritogenesis) with myogenesis itself remain unclear, various neural factors including attractive and repulsive axon-guidance cue ligands may be involved. Our previous studies proposed a heretofore unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) triggered its expression exclusively at the early-differentiation phase. In order to verify this concept, the present study was designed to clarify a paracrine source of HGF release. In vitro experiments demonstrated that activated anti-inflammatory macrophages (CD206-positive M2) produce HGF and thereby promote myoblast chemoattraction and Sema3A expression. Media from pro-inflammatory macrophage cultures (M1) did not show any significant effect. M2 also enhanced the expression of myoblast-differentiation markers in culture, and infiltrated predominantly at the early-differentiation phase (3-5 d post-injury); M2 were confirmed to produce HGF as monitored by in vivo/ex vivo immunocytochemistry of CD11b/CD206/HGF-positive cells and by HGF in situ hybridization of cardiotoxin- or crush-injured tibialis anterior muscle, respectively. Findings, therefore, encourage the idea that M2 contribute to spatiotemporal up-regulation of extracellular Sema3A concentrations by producing HGF that, in turn, stimulates a burst of Sema3A secretion by myoblasts that are recruited to site of injury. This model may ensure a coordinated delay in re-attachment of motoneuron terminals onto damaged fibers early in muscle regeneration, and thus synchronize the recovery of muscle-fiber integrity after injury.
(Key Words: Mouse muscle, Activated macrophages, Hepatocyte growth factor (HGF), Semaphorin 3A (Sema3A), Regenerative moto-neuritogenesis).
10. Tatsumi, R.,* Sakaguchi, S.,* Shono, J.,* Suzuki, T.,* Sawano, S., Anderson, J.E., Do, M.-K.Q., Ohtsubo, H., Mizunoya, W., Nakamura, M., Furuse, M., and Ikeuchi, Y. (*equal contributors), M2 macrophages may implicate in regenerative moto-neuritogenesis, by promoting myoblast migration and Sema3A expression, 2014 FASEB Science Research Conference on “Skeletal Muscle Satellite and Stem Cells” Steamboat Springs, CO, USA (July 20-25, 2014), 2014.07, Successful regeneration and remodeling of neuromuscular connections are critical for restoring functional properties of muscle fiber contractility. While the spatiotemporal regulatory mechanisms coordinating these processes (moto-neuritogenesis) with myogenesis itself remain unclear, various neural factors including attractive and repulsive axon-guidance cue ligands and their membrane receptors may be involved. Our previous studies proposed a heretofore unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) triggered its expression exclusively at the early-differentiation phase (Tatsumi et al., 2009; Do et al., 2011, 2012; Sato et al., 2013; Suzuki et al., 2013). In order to verify this concept, the present study was designed to clarify a paracrine source of HGF release. In vitro experiments demonstrated that activated anti-inflammatory macrophages (CD206-positive M2) produce HGF and thereby promote myoblast chemoattraction and Sema3A expression. Media from pro-inflammatory macrophage cultures (CD86-positive M1) did not show any significant effect. M2 infiltrated predominantly at the early-differentiation phase (3-5 d post-injury) and enhanced the expression of myoblast-differentiation markers; M2 were confirmed to produce HGF as monitored by in vivo/ex vivo immunocytochemistry of CD11b/CD206/HGF-positive cells and by HGF in situ hybridization of cardiotoxin- or crush-injured tibialis anterior muscle, respectively. Findings, therefore, encourage the idea that M2 contribute to spatiotemporal up-regulation of extracellular Sema3A concentrations by producing HGF that, in turn, stimulates a burst of Sema3A secretion by myoblasts that are recruited to site of injury. This regulatory axis of “M2 macrophages → satellite cell-derived myoblasts → intramuscular motoneuron terminals” may ensure a coordinated delay in attachment of motoneuron terminals onto regenerating/generating (new) fibers early in muscle regeneration, and thus synchronize the recovery of muscle-fiber integrity after injury..
11. Suzuki, T., Ohya, Y., Ojima, K., Mizunoya, W., Sawano, S., Ohtsubo, H., Nishimatsu, S., Anderson, J. E., Do, M.-K. Q., Nakamura, M., Furuse, M., Ikeuchi, Y., Nohno, T., and Tatsumi, R., Sema3A secreted from satellite cells promotes slow-twitch fiber generation, 2014 FASEB Science Research Conference on “Skeletal Muscle Satellite and Stem Cells” Steamboat Springs, CO, USA (July 20-25, 2014), 2014.07.
12. Ryuichi Tatsumi, Investigating muscle regeneration: The secret of Sema3A, International Innovation, 139, 89-91, 2014.06, Sema3A is a multifunctional molecule involved in several significant processes, but studies have so far neglected its potential impact in muscle biology. Research from Kyushu University in Japan is beginning to unravel its important role and results to date are promising..
13. Shohei Sakaguchi, Jun-ichi Shono, Takahiro Suzuki, Shoko Sawano, Judy E. Anderson, Mai-Khoi Q. Do, Hideaki Ohtsubo, Wataru Mizunoya, Yusuke Sato, Mako Nakamura, Mitsuhiro Furuse, Koji Yamada, Yoshihide Ikeuchi, Ryuichi A Tatsumi, Implication of anti-inflammatory macrophages in regenerative moto-neuritogenesis: promotion of myoblast migration and neural chemorepellent semaphorin 3A expression in injured muscle, International Journal of Biochemistry and Cell Biology, 10.1016/j.biocel.2014.05.032, 54, 272-285, 2014.06, Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed a heretofore unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) triggered its expression exclusively at the early-differentiation phase. In order to verify this concept, the present study was designed to clarify a paracrine source of HGF release. In vitro experiments demonstrated that activated anti-inflammatory macrophages (CD206-positive M2) produce HGF and thereby promote myoblast chemoattraction and Sema3A expression. Media from pro-inflammatory macrophage cultures (M1) did not show any significant effect. M2 also enhanced the expression of myoblast-differentiation markers in culture, and infiltrated predominantly at the early-differentiation phase (3-5 days post-injury); M2 were confirmed to produce HGF as monitored by in vivo/ex vivo immunocytochemistry of CD11b/CD206/HGF-positive cells and by HGF in situ hybridization of cardiotoxin- or crush-injured tibialis anterior muscle, respectively. These studies advance our understanding of the stage-specific activation of Sema3A expression signaling. Findings, therefore, encourage the idea that M2 contribute to spatiotemporal up-regulation of extracellular Sema3A concentrations by producing HGF that, in turn, stimulates a burst of Sema3A secretion by myoblasts that are recruited to site of injury. This model may ensure a coordinated delay in re-attachment of motoneuron terminals onto damaged fibers early in muscle regeneration, and thus synchronize the recovery of muscle-fiber integrity and the early resolution of inflammation after injury..
14. Jun-ichi Shono, Shohei Sakaguchi, Takahiro Suzuki, Mai-Khoi Q. Do, Wataru Mizunoya, Mako Nakamura, Yusuke Sato, Mitsuhiro Furuse, Koji Yamada, Yoshihide Ikeuchi, Ryuichi A Tatsumi, Preliminary Time-Course Study of Antiinflammatory Macrophage Infiltration in Crush-Injured Skeletal Muscle, Animal Science Journal, 10.1111/asj.12105, 84, 11, 744-750, 2013.11, Muscle damage induces massive macrophage infiltration of the injury site, in which activated proinflammatory and antiinflammatory phenotypes (currently classified as M1 and M2, respectively) have been documented as distinct functional populations predominant at different times after the conventional acute injury by intramuscular injection of snake venoms (cardiotoxin, notexin) or chemicals (bupivacaine hydrochloride, barium chloride). The present study employed a muscle-crush injury model that may reflect the more physiologic damage and repair processes initiated by contusing a gastrocnemius muscle in lower hind-limb of adult mice with hemostat forceps, and examined the time-course invasion of M1 and M2 macrophages during muscle regeneration by immunocytochemistry of CD197 and CD206 marker proteins. CD197-positive M1 macrophages were observed exclusively at 1-4 days after crush followed by the alternative prevalence of CD206-positive M2 at 7-days of myogenic differentiation time-point characterized by increasing levels of myogenin mRNA expression. Preliminary PCR analysis showed that M2 may produce hepatocyte growth factor (HGF) in culture, providing additional benefit to understanding that M2 populations actively promote regenerative myogenesis (muscle fiber repair) and moto-neuritogenesis (re-attachment of motoneuron terminals onto damaged fibers) through their time-specific infiltration and release of the growth factor at the injury site early in muscle regeneration. .
15. Takahiro Suzuki, Koichi Ojima, Mai-Khoi Q. Do, Minako Hara, Wataru Mizunoya, Mako Nakamura, Yoshihide Ikeuchi, Judy E. Anderson, Ryuichi Tatsumi, Semaphorin 3A secreted from myogenic stem cells promotes slow-twitch muscle fiber generation, 2013 EMBO Workshop on “Semaphorin Function and Mechanism in Action”, Cemay-la-Ville, France (October 29-31, 2013), 2013.10, Semaphorin 3A (Sema3A), a class 3 vertebrate-secreted semaphorin originally characterized as a potent neural chemorepellent, is now recognized to play crucial roles in angiogenesis, organogenesis, osteoclastogenesis and immune responses as a multi-functional modulator. Recently, we found that resident myogenic stem cells, satellite cells, up-regulate Sema3A expression and secretion exclusively at the early-myogenic differentiation phase in response to in vivo crush injury and hepatocyte growth factor treatment in the primary cultures (Tatsumi et al., 2009); however, its physiological significance in muscle regeneration is still unknown. Here we show that Sema3A impacts slow-type myosin heavy chain (slow-MyHC) expression in mouse satellite cell cultures. Sema3A-siRNA transfection significantly reduced expression of slow-MyHC as well as the muscle-specific transcription factor myogenin, and the down-stream mediators MEF2 as revealed by qPCR and western blotting analyses. Total MyHC expression level was unchanged, likely due to compensatory up-regulation of fast-MyHC during the 72-hr transfection period. Similar responses (except for fast-MyHC) were also observed in myogenin-knockdown cultures. In addition, reduced myogenin expression induced by immunoneutralization of the receptor neuropilin1 (Npn1) was rescued by co-addition of Sema3A protein. These results therefore indicate that Sema3A may activate a slow-MyHC expression-signaling axis consisting of Npn1, myogenin and MEF2. This model is supported by our comparative observations that satellite cells from soleus muscle (abundant in slow fibers) showed higher expression of Sema3A, myogenin and a co-receptor plexinA2 than those from EDL (Suzuki et al. 2013). Overall, the findings highlight a heretofore unexplored and active role for satellite cell-derived Sema3A as a key modulator of slow fiber generation during muscle regeneration, and advance our understanding of the multi-functional contributions of Sema3A..
16. Ryuichi Tatsumi, Judy E. Anderson, Ronald E. Allen, Muscle regeneration dynamics mediated by resident myogenic stem cells: a possible implication in moto-neuritogenesis and fiber-type regulation, Tucson Symposium 2013 on “The Biology of Muscle Growth and Repair”, 2013.09, Skeletal muscle regeneration and work-induced hypertrophy are initiated by mechanical insult or other perturbation and one of the earliest events is triggering the activation (re-entry to cell cycle from G0) of quiescent resident myogenic stem cells, satellite cells. Recent studies of satellite cells in culture and in vivo addressed the possible dual-roles of hepatocyte growth factor (HGF) in the stretch-induced activation and the re-establishing quiescence. In the proposed scenario, the time-coordinated increase in extracellular HGF is a key modulator for the two contrary pathways having low and high thresholds to impact activation and the counterpart quiescence of satellite cells, respectively. Moreover, the role of HGF in muscle repair may not be restricted to myogenesis; we demonstrated that HGF up-regulates expression of secreted axon-guidance molecule semaphorin 3A (Sema3A) in satellite cells at early-differentiation phase in primary cultures and in vivo. The results encourage a possible implication of satellite cells in the spatiotemporal regulation of extracellular Sema3A concentrations, which potentially mediates restoration or remodeling of nerve-muscle connections in muscle regeneration in synchrony with recovery of muscle-fiber integrity and types (fast and slow). Very recently, we found in satellite cell cultures that the Sema3A ligand impacts slow-twitch fiber generation through a muscle-specific transcription factor myogenin-dependent pathway; Sema3A-siRNA transfection significantly reduced expression of slow-type myosin heavy chain (slow-MyHC) as well as myogenin and its co-mediator MEF2. Total MyHC protein expression level was likely unchanged, due to compensatory up-regulation of fast-MyHC and similar responses (except for fast-MyHC) were also observed in myogenin-knockdown cultures. Overall our results highlight the “programmed mechano-biology dynamics” that successful muscle regeneration, comprised of satellite cell-driving myogenesis, intramuscular moto-neuritogenesis and fiber-type regulation (survival), may be a programmed sequence of events that respond to a mechanical perturbation in a synchronous, HGF-dependent and time-coordinated manner..
17. Yusuke Sato, Mai-Khoi Q. Do, Takahiro Suzuki, Hideaki Ohtsubo, Wataru Mizunoya, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Ryuichi A Tatsumi, Satellite Cells Produce Neural Chemorepellent Semaphorin 3A upon Muscle Injury, Animal Science Journal, 10.1111/asj.12104, 84, 185-189, Listed on ScienceAlerts.com, 2013.02, Regenerative mechanisms that regulate intramuscular motor innervation including configuration of the neuromuscular connections are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed a heretofore unexplored role of satellite cells as a key source of a secreted neural chemorepellent semaphorin 3A (Sema3A) expression. In order to verify this concept, there is still a critical need to provide direct evidence to show the up-regulation of Sema3A protein in satellite cells in vivo upon muscle injury. The present study employed a Sema3A/MyoD double-immunohistochemical staining for cryo-sections prepared from cardiotoxin (CTX)-injected gastrocnemius muscle of adult mouse lower hind-limb. Results clearly demonstrated that Sema3A expression was up-regulated in MyoD-positive satellite cells at 4-12 days post-injury period, the time that corresponds to the cell differentiation phase characterized by increasing myogenin mRNA expression. This direct proof encourages a possible implication of satellite cells in the spatiotemporal regulation of extracellular Sema3A concentrations, which potentially ensures coordinating a delay in neurite sprouting and re-attachment of motoneuron terminals onto damaged muscle fibers early in muscle regeneration in synchrony with recovery of muscle-fiber integrity..
18. Takahiro Suzuk, Mai-Khoi Q. Do, Yusuke Sato, Koichi Ojima, Minako Hara, Wataru Mizunoya, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Judy E. Anderson, Ryuichi A Tatsumi, Comparative Analysis of Semaphorin 3A in Soleus and EDL Muscle Satellite Cells In Vitro toward Understanding Its Role in Modulating Myogenin Expression, International Journal of Biochemistry and Cell Biology, 45, 2, 476-482, Listed on ScienceAlerts.com, 2013.02, Resident myogenic stem cells, satellite cells, up-regulate a secreted multi-functional modulator, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle-crush injury and treatment with hepatocyte growth factor (HGF) or basic fibroblast growth factor (FGF2). Here, we add evidence that the Sema3A expression and secretion induced by the growth factors is significantly higher in primary cultures from adult rat soleus than from the fast-twitch extensor digitorum longus (EDL) muscle. The higher Sema3A response, revealed by quantitative PCR and western blotting of cell lysates and conditioned media, may account for the higher myogenin expression of soleus muscle satellite cells early in differentiation since addition of recombinant Sema3A stimulates myogenin expression in cultures. These experiments also showed that mRNA expression of plexin A2, which together with neuropilins, constitutes Sema3A composite-receptors, was higher in satellite cells from soleus than EDL with no difference in plexin A1 and A3 and neuropilin-1 and 2 levels. These comparative studies, therefore, highlight a possible Sema3A-plexin A2-myogenin signaling axis that may ensure promoting early differentiation by soleus muscle satellite cells. .
19. Mai-Khoi Q. Do, Takahiro Suzuki, Borjigin Gerelt, Yusuke Sato, Wataru Mizunoya, Mako Nakamura, Yoshihide Ikeuchi, Judy E. Anderson, and Ryuichi Tatsumi, Time-Coordinated Prevalence of Extracellular HGF, FGF2 and TGF-β3 in Crush-Injured Skeletal Muscle, Animal Science Journal, 83, 712-717, 2012.10, Successful regeneration and remodeling of neuromuscular junctions are critical for restoring functional capacities and properties of skeletal muscle after damage, and axon-guidance molecules may be involved in the signaling that regulates such restoration. Recently, we found that early-differentiated satellite cells up-regulate a secreted neural chemorepellent Sema3A upon in vivo muscle-crush injury. The study also revealed that Sema3A expression is up-regulated in primary satellite-cell cultures in response to hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) and prevented by transforming growth factor (TGF)-β2, 3 (Tatsumi et al. 2009. Am J Physiol Cell Physiol; Do et al. 2011. Am J Physiol Cell Physiol). In order to verify the physiological significance of this regulation in vitro, the present study was designed to estimate the time-course of extracellular HGF, FGF2 and TGF-β3 concentrations after crush-injury of gastrocnemius muscle in the rat lower hind-limb, using a combination of a non-homogenization/non-spin extraction of extracellular wound fluids and ECL-western blotting analyses. Results clearly demonstrated that active HGF and FGF2 are prevalent in 2-8 days post-crush, whereas active TGF-β3 increases after 12 days, providing a better understanding of the time-coordinated levels of HGF, FGF2, and TGF-β3 that drive regulation of Sema3A expression during regenerative intramuscular moto-neuritogenesis..
20. Tatsumi, R.,* Hara, M.,* Tabata, K.,* Suzuki, T., Do, M.-K. Q., Mizunoya, W., Nakamura, M., Ikeuchi, Y., Anderson, J. E., and Allen, R. E. (*equal contributors), Mechano-Sensing Calcium-Influx Machinery that Instigates Skeletal Muscle Satellite Cell Activation, 2012 FASEB Science Research Conference on “Skeletal Muscle Satellite & Stem Cells", Lucca, Italy, 2012.08, When skeletal muscle is stretched or injured, satellite cells, resident myogenic stem cells positioned beneath the basal lamina of mature muscle fibers, are activated to enter the cell cycle. This signaling pathway is a cascade of events including calcium-calmodulin formation, nitric oxide (NO) radical production by NO synthase, matrix metalloproteinase activation, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the receptor c-met, as demonstrated by assays of primary cultures and in vivo experiments. Here, we add evidence that two ion channels, the mechano-sensitive cation channel (MS-channel) and the long-lasting-type voltage-gated calcium-ion channel (L-VGC-channel), mediate the influx of extracellular calcium ions in response to cyclic stretch in satellite-cell cultures. When applied to 1-hr stretch cultures with individual inhibitors for MS- and L-VGC-channels (GsMTx-4 and nifedipine, respectively) or with a less specific inhibitor for MS-channels (gadolinium chloride, Gd), satellite cell activation and upstream HGF release were abolished, as revealed by bromodeoxyuridine-incorporation assays and western blotting of conditioned media, respectively. The inhibition was dose-dependent with a maximum at 0.1 μM (GsMTx-4), 10 μM (nifedipine) or 100 μM (Gd) and cancelled by addition of HGF to the culture media; a potent inhibitor for transient-type VGC-channels (NNC55-0396, 100 μM) did not show any significant inhibitory effect. The stretch response was also abolished when calcium-chelator EGTA (1.8 mM) was added to the medium, indicating the significance of extracellular free calcium ions in our present activation model. Finally, cation/calcium channel dependencies were further documented by calcium-imaging analyses on stretched cells; results clearly demonstrated that calcium ion influx was abolished by GsMTx-4, nifedipine and EGTA. Therefore, these results provide an additional insight that calcium ions may flow in through L-VGC-channels by possible coupling with adjacent MS-channel gating that promotes the local depolarization of cell membranes to impact the satellite cell activation cascade..
21. Suzuki, T., Ojima, K., Do, M.Q., Hara, M., Mizunoya, W., Nakamura, M., Ikeuchi, Y., Anderson, J.E. and Tatsumi, R., Semaphorin 3A regulates the early differentiation of satellite cells, 2012 FASEB Science Research Conference on “Skeletal Muscle Satellite & Stem Cells", Lucca, Italy, 2012.08, Semaphorin 3A (Sema3A), a class 3 vertebrate-secreted semaphorin, is a potent axon-guidance molecule for sensory, sympathetic and motor neurons. Recently, we found that resident myogenic stem cells, satellite cells, up-regulate Sema3A expression and secretion exclusively at the early-myogenic differentiation phase in response to in vivo crush injury and HGF/FGF2 treatments in the primary cultures, suggesting possible implication of satellite cells in regenerative motoneuritogenesis including sprouting and attachment of motoneuron terminals onto damaged muscle fibers in synchrony with recovery of muscle-fiber structures (Tatsumi et al., Am. J. Physiol. Cell Physiol. 2009; Do et al., Am. J. Physiol. Cell Physiol. 2011). Here, we show that Sema3A also mediates post-natal myogenesis by stimulating the early differentiation of satellite cells. When recombinant Sema3A (R&D Systems) was added to satellite cell cultures for 24 hr from 48-hr post-plating, myogenin message (an early differentiation marker) was up-regulated in a dose-dependent manner with a maximum at 10 ng/ml. Sema3A-specific knock-down by RNAi technique (about 60-75% reduction efficiency) remarkably down-regulated myogenin expression at message and protein levels at the early-differentiation stage, however showed no significant effect on MyoD expression at the same phase and myosin heavy chain expression and myotube formation at the later stage. Immunofluorescence analysis revealed the presence of Sema3A membrane-receptor neuropilin1 (Npn1) at 48-hr post-plating, which is the early-differentiation time-point which siRNA was transfected to cells; immunoneutralization of Npn1 activity also reduced the myogenin expression, which can be rescued competitively by co-addition of Sema3A protein, to a level equivalent to control cultures without anti-Npn1 antibody and Sema3A. These results indicate that satellite cell-secreted Sema3A may bind to the receptor Npn1 to generate myogenin expression signaling that stimulates early differentiation of satellite cells in autocrine and/or paracrine fashions. This topic may be supported potentially by our comparative observations that rat soleus muscle satellite cells showed higher expression activities of Sema3A, myogenin, and plexinA2 (a signaling co-receptor protein for Sema3A) than EDL muscle cells at the early-differentiation stage. Overall, the data highlight again a heretofore unexplored and active role for Sema3A as a key regulator of the early myogenic differentiation of satellite cells during muscle regeneration, therefore providing a better understanding of multi-functional contributions of Sema3A..
22. Do, M.Q., Shimizu, N., Suzuki, T., Mizunoya, W., Nakamura, M., Ikeuchi, Y., Anderson, J.E. and Tatsumi, R., Heparan/chondroitin sulfate chains may mediate HGF/FGF2-induced up-regulation of neural chemorepellent Sema3A in satellite cell cultures, 2012 FASEB Science Research Conference on “Skeletal Muscle Satellite & Stem Cells", Lucca, Italy, 2012.08, Semaphorin 3A (Sema3A, also referred to as SemaIII, SemD and collapsin), a class 3 vertebrate-secreted semaphorin, is a potent axon-guidance cue for sensory, sympathetic and motor axons. Recently, we found that satellite cells up- or down-regulate Sema3A in time-dependent responses to in vivo muscle crush-injury and in vitro treatment with recombinant HGF, FGF2 or TGF-βs. Such responses imply that satellite cells are involved in regenerative motoneuritogenesis, including sprouting and re-attachment of motoneuron terminals onto damaged muscle fibers. In order to explore the mechanism of HGF/FGF2-induced Sema3A up-regulation, the present study was designed to investigate possible membrane receptors that are present on satellite cells and could be involved in that signaling pathway. First, we tested whether c-met and FGFR1, high-affinity receptors of HGF and FGF2 respectively, are responsible for Sema3A up-regulation. Treatment with anti-c-met and anti-FGFR1 neutralizing antibodies did not diminish Sema3A up-regulation, indicating that c-met and FGFR1 may not mediate the response. In addition to such high-affinity receptors, HGF and FGF2 also bind with lower affinity to glycosaminoglycan (GAG) chains of proteoglycans - an important component of extracellular matrix- for a variety of biological functions. We therefore hypothesized that the association between HGF/FGF2 and GAG chains might mediate the Sema3A up-regulation. To test the hypothesis, satellite cell cultures were pretreated with GAG-degrading enzymes before the addition of HGF or FGF2, and the level of Sema3A expression was quantified by real-time qPCR. Results showed that treatment with heparitinase for partial removal of heparan sulfate chains significantly decreased induction of Sema3A up-regulation by HGF, but not FGF2. Similarly, treatment with chondroitinase ABC for partial removal of chondroitin sulfate chains significantly diminished the Sema3A up-regulation induced by FGF2, but not HGF. These results suggest that HGF and FGF2 bind to receptors carrying heparan and/or chondroitin sulfate chains; syndecans or other transmembrane-type proteoglycans appear to be plausible receptor candidates for signaling via growth factors to up-regulate Sema3A in satellite cells in culture. .
23. Komiya, Y., Mizunoya, W., Anderson, J.E., Goto, T., Takahashi, N., Kawada, T., Sato, Y., Nakamura, M., Tatsumi, R., and Ikeuchi, Y., Change of skeletal muscle fiber types by n-3 poly unsaturated fatty acid, 2012 FASEB Science Research Conference on “Skeletal Muscle Satellite & Stem Cells", Lucca, Italy, 2012.08, Skeletal muscle fibers are classified as type I (red/oxidative/slow) and type II (white/glycolytic/fast) based on color, metabolism and contractile properties. Type I fibers are especially mitochondria-rich and use oxidative metabolism for energy production. Thus, an increase of type I fibers can counteract obesity and reduce fatigue. In a recent study, the nuclear receptor peroxisome proliferator-activated receptor (PPAR) δ attracted attention as a factor regulating muscle fiber type. Over-expression of activated PPARδ caused a shift to slow-type fibers (Wang et al. 2004, PLoS Biol., 2: 1532-1539) and polyunsaturated fatty acid (PUFA) has the ligand activity of PPARδ (Forman et al. 1996, Ann. N.Y.Acad.Sci., 804: 266-275). Recently, we found in rat skeletal muscle that fiber type distribution was slower in vivo after feeding with fish oil. To elucidate this phenomenon, we hypothesized that the change to slow muscle with fish oil results from fish oil PUFA activating the receptor activity of PPARδ. Here, we tested the hypothesis using a rat muscle fiber culture assay. Since muscle fiber-type transformation generally occurs in mature fibers, this culture model has the advantage that fibers can express mature MyHC isoforms while differentiated cell lines such as C2C12 and L6 cannot. Rat fiber cultures were established according to the mouse protocol (Wozniak and Anderson 2005, Biochem.Cell Biol., 83: 674-676) and over 90% muscle fibers were alive until 7 days of culture. When the PPARδ−specific agonist (GW501516) was added to fibers cultured for 7 days, transcript expression of MyHC1and 2A was up-regulated at day 1, lipoprotein lipase message was up-regulated at day 3, and pyruvate dehydrogenase kinase (PDK) 4 and uncoupling protein 3 were up-regulated at day 7. Using luciferase reporter assays, PPARδ ligand activity was measured for several kinds of fatty acid. Results showed that, eicosapentaenoic acid (EPA), abundant in fish oil, had higher ligand activity to PPARδ compared with other fatty acids. When EPA was added to fiber cultures for 24 hours, PDK4 mRNA was up-regulated. In addition, when both EPA and PPARδ-specific antagonist (GSK0660) were added to fiber cultures, the up-regulation of PDK4 mRNA by addition of EPA was reseted to the control level. In conclusion, EPA up-regulates a protein characteristic of slow-type muscle via PPARδ activation and may transform muscle fiber type into slow type. .
24. Minako Hara, Kuniko Tabata, Takahiro Suzuki, Mai-Khoi Q. Do, Wataru Mizunoya, Mako Nakamura, Shotaro Nishimura, Shoji Tabata, Yoshihide Ikeuchi, Kenji Sunagawa, Judy E. Anderson, Ronald E. Allen, and Ryuichi Tatsumi, Calcium Influx through a Possible Coupling of Cation Channels Impacts Skeletal Muscle Satellite Cell Activation in Response to Mechanical Stretch, American Journal of Physiology-Cell Physiology, 2012年3月26日掲載受理、セットで先行公開, 2012.03.
25. Do, M.-K. Q., Sato, Y., Shimizu, N., Suzuki, T., Shono, J.-I., Mizunoya, W., Nakamura, M., Ikeuchi, Y., Anderson, J. E., and Tatsumi, R., Growth Factor Regulation of Neural Chemorepellent Sema3A Expression in Satellite Cell Cultures, American Journal of Physiology-Cell Physiology, 301, C1270-C1279, Listed on the March edition of Global Medical Discovery Series, 2011.11, 筋肥大・再生において筋幹細胞(衛星細胞)が合成・分泌する神経軸索ガイダンス因子Sema3Aによって運動神経末端の再接着(神経支配の回復)が制御されていることをはじめて見出した他、このSema3Aの発現がHGF/FGF2/TGF-beta2,3によって時系列的に調節されていることを示した。.
26. Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Hattori, A., Anderson, J. E., and Allen, R. E., Mechano-Biology of Resident Myogenic Stem Cells: Implication in Postnatal Myogenesis and Intramuscular Motoneuritogenesis, Animal Science Congress 2010 of the Asian-Australian Association of Animal Production Societies (AAAP), National Pingtung University of Science and Technology (NPUST), Pingtung, Taiwan , 2010.08.
27. Tatsumi, R.,* Do, M.-K. Q.,* Shimizu, N.,* Sankoda, Y.,* Anderson, J. E., Sato, Y., Suzuki, T., Mizunoya, W., Ikeuchi, Y., and Allen, R. E. (*equal contributors), Possible Implication of Satellite Cells in Regenerative Motoneuritogenesis: HGF and FGF2 Upregulate Neural Chemorepellent Sema3A Expression, Theme 3: Tissue Mechanics, Track 3.6 Muscle Mechanics and Motor Control, at the 6th World Congress on Biomechanics (WCB) 2010, in conjunction with the 14th International Conference on Biomedical Engineering (ICBME) 2010 and the 5th Asian Pacific Conference on Biomechanics (APBiomech) 2010, Suntec Convention and Exhibition Center, Singapore , 2010.08, 筋肥大・再生の過程で、筋幹細胞(衛星細胞)が肝細胞増殖因子HGF依存的に神経軸索ガイダンス因子Sema3Aを合成・分泌することを見出し、衛星細胞が運動神経末端の再接着制御に能動的に関与している可能性を提起した。このアイデアが評価され、掲載雑誌のEditorial Focusに選定された。.
28. Tatsumi, R., Anderson, J. E. and Allen, R. E.., Mechano-Biology on Stretch-Induced Activation of Resident Myogenic Stem Cells, Symposium on “Muscle Injury” section at the 6th World Congress on Biomechanics (WCB) 2010, in conjunction with the 14th International Conference on Biomedical Engineering (ICBME) 2010 and the 5th Asian Pacific Conference on Biomechanics (APBiomech) 2010, Suntec Convention and Exhibition Center, Singapore , 2010.08, In undamaged postnatal muscle fibers with normal contraction and relaxation activities, quiescent satellite cells of resident
myogenic stem cells are interposed between the overlying external lamina and the sarcolemma of a subjacent mature
muscle fiber. When muscle is injured, exercised, overused or mechanically stretched, these cells are activated to enter the
cell proliferation cycle, divide, differentiate, and fuse with the adjacent muscle fiber, and are responsible for regeneration
and work-induced hypertrophy of muscle fibers. Therefore, a mechanism must exist to translate mechanical changes in
muscle tissue into chemical signals that can activate satellite cells. Recent studies of satellite cells or single muscle fibers in
culture and in vivo demonstrated the essential role of hepatocyte growth factor (HGF) and nitric oxide (NO) radical in the
activation pathway. These experiments have also reported that mechanically stretching satellite cells or living skeletal
muscles triggers the activation by rapid release of HGF from its extracellular tethering and the subsequent presentation to
the receptor c-met. HGF release has been shown to rely on calcium-calmodulin formation and NO radical production in
satellite cells and/or muscle fibers in response to the mechanical perturbation, and depend on the subsequent
up-regulation of matrix metalloproteinase (MMP) activity. These results indicate that the activation mechanism is a cascade
of events including calcium ion influx, calcium-calmodulin formation, NO synthase activation, NO radical production, MMP
activation, HGF release and binding to c-met. Better understanding of ‘mechano-biology’ on the satellite cell activation is
essential for designing procedures that could enhance muscle growth and repair activities in meat-animal agriculture and
also in neuromuscular disease and aging in humans..
29. Do, M.-K. Q.,* Shimizu, N.,* Sato, Y., Suzuki, T., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Anderson, J. E., and Allen, R. E. (*equal contributors), Possible Implication of Satellite Cells in Regenerative Motoneuritogenesis: Temporal Coordination of HGF/FGF-2/TGF-beta may Regulate Neural Chemorepellent Sema3A expression, 2010 FASEB Summer Research Conference on “Skeletal Muscle Satellite & Stem Cells", Carefree, AZ, US, 2010.07, 筋肥大・再生の過程で、筋幹細胞(衛星細胞)が肝細胞増殖因子HGF依存的に神経軸索ガイダンス因子Sema3Aを合成・分泌することを見出し、衛星細胞が運動神経末端の再接着制御に能動的に関与している可能性を提起した。このアイデアが評価され、掲載雑誌のEditorial Focusに選定された。.
30. Suzuki, T., Takaishi, H., Sakata, T., Do, M. Q., Hara, M., Sato, A., Mizunoya, W., Nishimura, T, Hattori, A., Ikeuchi, Y., and Tatsumi, R., In Vitro Measurement of Postnatal Changes in Proliferating Satellite Cell Frequency during Rat Muscle Growth, Animal Science Journal, 81, 2, 245-251, 2010.04.
31. Sato, Y., Probst, H. C., Tatsumi, R., Ikeuchi, Y., Neuberger, M. S., and Rada, C., Deficiency in APOBEC2 Leads to a Shift in Muscle Fiber Type, Diminished Body Mass and Myopathy, Journal of Biological Chemistry, 285, 7111-7118 , 2010.03.
32. Yamada, M., Tatsumi, R., Yamanouchi, K., Hosoyama, T., Shiratsuchi, S., Sato, A., Mizunoya, W., Ikeuchi, Y., Furuse, M., and Allen, R. E. , High Concentrations of HGF Inhibit Skeletal Muscle Satellite Cell Proliferation In Vitro By Inducing Expression of Myostatin: A Possible Mechanism for Re-Establishing Satellite Cell Quiescence In Vivo. , American Journal of Physiology-Cell Physiology, 298, C465–C476 , Editorial Focusに選定, 2010.03, 骨格筋の肥大・再生は筋幹細胞である衛星細胞の増殖活性に依存しており、これは衛星細胞の活性化と休止化のバランスによって制御されている。これまでに、肝細胞増殖因子HGFによる衛星細胞の活性化機構を明らかにしてきたが、これと逆反応の休止化もまたHGFによって誘導されることを見出した。物理刺激をトリガーにして、HGF濃度依存的に衛星細胞が活性化・増殖した後に自立的に休止化するという、独創的な時系列進行モデルを提起した。.
33. Ryuichi A Tatsumi, Mechano-Biology of Skeletal Muscle Hypertrophy and Regeneration: Possible Mechanism of Stretch-Induced Activation of Resident Myogenic Stem Cells, Animal Science Journal, 81, 11-20, invited review, 2010.01, 筋幹細胞である衛星細胞が物理刺激を引き金として活性化・増殖し筋肥大・再生に寄与する分子メカニズムを解明した一連の研究を、Animal Science Jouranlの招待総説論文として発表した。.
34. Ryuichi Tatsumi, Yoriko Sankoda, Judy E. Anderson, Yusuke Sato, Wataru Mizunoya, Naomi Shimizu, Takahiro Suzuki, Michiko Yamada, Robert P. Rhoads, Jr., Yoshihide Ikeuchi, and Ronald E. Allen, Possible Implication of Satellite Cells in Regenerative Motoneuritogenesis: HGF Up-Regulates Neural Chemorepellent Sema3A during Myogenic Differentiation, American Journal of Physiology-Cell Physiology, 297, C238-C252, Editorial Focusに選定, 2009.08.
35. Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., Buchman, V. L., and Ikeuchi, Y. , Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy, Bioscience, Biotechnology and Biochemistry, 73, 1748-1756, 2009年度BBB論文賞を受賞, 2009.06.
36. Sato, Y., Shimizu, M., Mizunoya, W., Tatsumi, R., Probst, H., Rada, C., Neuberger, M. S., and Ikeuchi, Y., Skeletal Muscle Fiber Type Change and Myopathy in APOBEC-2 KO Mouse, A Joint meeting of Frontiers in Myogenesis and Skeletal Muscle Satellite and Stem Cells, 2009.05.
37. Yamada, M., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., and Allen, R. E., HGF Induces Myostatin Expression and the Subsequent Satellite Cell Quiescence in a Neuropilin-1 Dependent Manner, A Joint meeting of Frontiers in Myogenesis and Skeletal Muscle Satellite and Stem Cells, 2009.05.
38. Tatsumi, R., Sankoda, Y., Anderson, J. E., Sato, Y., Mizunoya, W., Shimizu, N., Suzuki, T., Yamada, M., Rhoads, R. P., Jr., Ikeuchi, Y., and Allen, R. E. , A Possible Role for Satellite Cells in Regenerative Motoneurogenesis: HGF Up-Regulates Neural Chemorepellent Sema3A Expression, A Joint meeting of Frontiers in Myogenesis and Skeletal Muscle Satellite and Stem Cells, 2009.05.
39. Tatsumi, R., Wuollet, A. L., Tabata, K., Nishimura, S., Tabata, S., Mizunoya, W., Ikeuchi, Y., and Allen, R. E., A Role for Calcium-Calmodulin in Regulating Nitric Oxide Production during Skeletal Muscle Satellite Cell Activation, American Journal of Physiology-Cell Physiology, 296, C922-C929, 2009.03.
40. Yamada, M., Shiratsuchi, S.-I., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., and Allen, R. E., A Receptor Neuropilin-1 Mediates HGF-Induced Muscle Satellite Cell Quiescence, The American Society for Cell Biology 48th Annual Meeting, 2008.12.
41. Yamada, M., Sankoda, Y., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Sunagawa, K., and Allen, R. E., Matrix Metalloproteinase-2 Mediates Stretch-Induced Activation of Skeletal Muscle Satellite Cells in A Nitric Oxide Dependent Manner, International Journal of Biochemistry and Cell Biology, 40, 2183-2191., 2008.07.
42. Tatsumi, R. and Allen, R.E., Mechano-Biology of Resident Myogenic Stem Cells: Molecular Mechanism of Stretch-Induced Activation of Satellite Cells., Animal Science Journal, 79, 279-290; invited review, 2008.05, 筋幹細胞である衛星細胞が物理刺激を引き金として活性化・増殖し筋肥大・再生に寄与する分子メカニズムを解明した一連の研究を、招待総説論文に紹介した。本論文は2008年に掲載され、その後の論文引用回数などが評価され2011年度の優秀論文賞を受賞した。.
43. Yamada, M., Sankoda, Y., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., and Allen, R. E., Matrix Metalloproteinase-2 Is Involved In Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells., 2007 FASEB Summer Research Conference on “Skeletal Muscle Satellite & Stem Cells, 2007.07.
44. Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., and Ikeuchi, Y. , Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy., Adult Skeletal Muscle Symposium: Growth, Function and Motility , 2007.06.
45. Mizunoya, Y., Okamoto, S., Wakamatsu, J.-I., Sonoda, Y., Sekiguchi, T., Waga, T., Tatsumi, R., and Ikeuchi, Y. , Food Components Do Affect Skeletal Muscle Mass and Fiber Types: Effects of Beef Extract and Apple Polyphenol. , Adult Skeletal Muscle Symposium: Growth, Function and Motility , 2007.06.
46. Tatsumi, R., Yamada, M., Katsuki, Y., Okamoto, S., Ishizaki, J., Muzunoya, W., Ikeuchi, Y., Hattori, A., Shimokawa, H., and Allen, R. E., Low-pH Preparation of Skeletal Muscle Satellite Cells Can be Used to Study Activation In Vitro., International Journal of Biochemistry and Cell Biology, 38, 1678-1685, 2006.08.
47. Tatsumi, R., Liu, X., Pulido, A., Morales, M., Sakata, T., Dail, S., Hattori, A., Ikeuchi, Y., and Allen, R. E., Satellite Cell Activation in Stretched Skeletal Muscle and The Role of Nitric Oxide and Hepatocyte Growth Factor., American Journal of Physiology-Cell Physiology, 290, 1487-1494, 2006.06.
48. Yamada, M., Tatsumi, R., Kikuiri, T., Okamoto, S., Nonoshita, S., Mizunoya, W., Ikeuchi, Y., Shimokawa, H., Sunagawa, K., and Allen, R. E., Matrix Metalloproteinases are Involved in Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells., Muscle & Nerve, 34, 313-319, 2006.04.
49. Sakata, T., Tatsumi, R., Yamada, M., Shiratsuchi, S., Okamoto, S., Mizunoya, W., Hattori, A., and Ikeuchi, Y., Preliminary Experiments on Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells In Vivo., Animal Science Journal, 77, 518-525, 2006.04.
50. Yamada, M., Tatsumi, R., Okamoto, S., Nonoshita, S., Mizunoya, W., Ikeuchi, Y., and Allen, R. E., Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells Requires Matrix Metalloproteinase Activity., FRONTIERS IN MYOGENESIS, the meeting of the Society for Muscle Biology, 2006.04.
51. Ryuichi Tatsumi, Keitaro Yamanouchi, Toru Hosoyama, Sei-ichi Shiratsuchi, Michiko Yamada, Jun-ichiro Wakamatsu, Wataru Mizunoya, Yoshihide Ikeuchi, and Ronald E. Allen, A Possible Mechanism of Muscle Satellite Cell Quiescence: HGF Induces Myostatin Expression and Secretion., FASEB Summer Research Conference 2005, 4rd International Conference on Skeletal Muscle & Stem Cells, 2005.06.
52. Tatsumi, R. and Allen, R.E., Active Hepatocyte Growth Factor Is Present in Skeletal Muscle Extracellular Matrix, Muscle & Nerve, 10.1002/mus.20114, 30, 5, 654-658, 30, 654-658, 2004.11.
53. Mendias, C., Tatsumi, R., and Allen, R.E., Role of Cyclooxygenase-1 and -2 in Satellite Cell Proliferation, Differentiatio, and Fusion, Muscle & Nerve, 10.1002/mus.20102, 30, 4, 497-500, 30, 497-500, 2004.10.
54. Tatsumi, R., Mitsuhashi, K., Ashida, K., Haruno, A., Hattori, A., Ikeuchi, Y., and Allen, R.E., Comparative Analysis of Mechanical Stretch-Induced Activation Activity of Back and Leg Muscle Satellite Cells In Vitro, Animal Science Journal, 75, 345-351, 2004.08.
55. Tatsumi, R. and Allen, R.E., Satellite Cell Activation in Response to Muscle Stretch and Damage, FASEB Summer Research Conference 2003, 3rd International Conference on Muscle Satellite & Stem Cells, 2003.07.
56. Allen, R.E. and Tatsumi, R., Satellite Cell Activation in Response to Muscle Damage, Molecular Biology of Muscle Development and Regeneration, 2003.05.
57. Tatsumi, R., Hattori, A., Ikeuchi, Y., Anderson, J. E., and Allen, R. E., Release of Hepatocyte Growth Factor from Mechanical Stretched Skeletal Muscle Satellite Cells and the Role of pH and Nitric Oxide, Molecular Biology of the Cell, 10.1091/mbc.E02-01-0062, 13, 8, 2909-2918, 13, 2909-2918, 2002.12.
58. Tatsumi, R., Hattori, A., Allen, R. E., Ikeuchi Y., and Ito, T., Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells Is Dependent on Nitric Oxide Production, Animal Science Journal, 73, 235-239, 2002.12.
59. Tatsumi, R., Maeda, K., Hattori, A., and Takahashi, K., Calcium Binding to an Elastic Portion of Connectin/Titin Filaments, Journal of Muscle Research and Cell Motility, 22, 149-162, 2001.12.
60. Tatsumi, R., Sheehan, S. M., Iwasaki, H., Hattori, A., and Allen, R. E., Mechanical Stretch Induces Activation of Skeletal Muscle Satellite Cells In Vitro, Experimental Cell Research, 267, 107-114, 2001.12.
61. Tatsumi, R., Sakata, T., Sheehan, S.M., Hattori, A., and Allen, R.E., Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells: the Possible Role of HGF in the Mechanism, FASEB Summer Research Conference 2000, 2nd International Conference on Muscle Satellite & Stem Cells, 2001.07.
62. Sheehan, S. M., Tatsumi, R., Temm-Grove, C.J., and Allen, R. E., HGF is an Autocrine Growth Factor for Skeletal Muscle Satellite Cells In Vitro, Muscle & Nerve, 23, 239-245, 2000.12.
63. Tatsumi, R., Sheehan, S.M., Iwasaki, H., Hattori, A., and Allen, R.E., Mechanical Stretch Induces Activation of Skeletal Muscle Satellite Cells In Vitro., 2000 Keystone Symposia on the Molecular Biology of Muscle Development and Disease, 2000.05.
64. Tatsumi, R., Anderson, J. E., Nevoret, C. J., Halevy, O., and Allen, R. E., HGF/SF is Present in Normal Adult Skeletal Muscle and Is Capable of Activating Satellite Cells, Developmental Biology, 194, 114-128., 1998.12.
65. Allen, R.E. and Tatsumi, R., Satellite Cell Activation and the Role of Hepatocyte Growth Factor/Scatter Factor, Post-natal Myogenesis: Satellite Cells In Action, 1998.08.
66. Tatsumi, R., Shimada, K., and Hattori, A., Fluorescence Detection of Calcium-Binding Proteins with Quinoline Ca-Indicator Quin2, Analytical Biochemistry, 254, 126-131, 1997.01.
Presentations
1. 鈴木貴弘, 西松伸一郎, 寺田久美子, 片瀬直樹, 濃野 勉, 水野谷 航, 池内 義秀, 辰巳 隆一, 筋幹細胞特異的 Sema3A cKO マウスの解析, 第119回日本畜産学会大会, 2015.03.
2. ド マイコイ, 水野谷 航, 尾嶋孝一, 中村 真子, 池内 義秀, 辰巳 隆一, Sema3A ligand secreted from satellite cells promotes aneural nAChR clustering, 第119回日本畜産学会大会, 2015.03.
3. Shohei Sakaguchi, Junichi Shono, Takahiro Suzuki, Shoko Sawano, Judy E. Anderson, Mai-Khoi Q. Do, Hideaki Ohtsubo, Wataru Mizunoya, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Ryuichi Tatsumi, Anti-inflammatory macrophages implicate in regenerative moto-neuritogenesis, by promoting myoblast migration and Sema3A expression., Animal Science Congress 2014 of the Asian-Australian Association of Animal Production Societies (AAAP), 2014.11.
4. Ryuichi Tatsumi, Judy E. Andeson, Ronald E. Allen, Muscle regeneration dynamics: satellite cells may do more., A Meeting-of-Minds Muscle Symposium, 2014.09.
5. Ryuichi Tatsumi, Shohei Sakaguchi, Junichi Shono, Takahiro Suzuki, Shoko Sawano, Judy E. Anderson, Mai-Khoi Q. Do, Hideaki Ohtsubo, Wataru Mizunoya, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, M2 macrophages may implicate in regenerative moto-neuritogenesis, by promoting myoblast migration and Sema3A expression., 2014 FASEB Science Research Conference on “Skeletal Muscle Satellite and Stem Cells”, 2014.07.
6. Takahiro Suzuki, Yuki Ohya, Koichi Ojima, Wataru Mizunoya, Shoko Sawano, Hideaki Ohtsubo, Shinichiro Nishimatsu, Judy E. Anderson, Mai-Khoi Q. Do, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Tsutomu Nohno, Ryuichi Tatsumi, Sema3A secreted from satellite cells promotes slow-twitch fiber generation., 2014 FASEB Science Research Conference on “Skeletal Muscle Satellite and Stem Cells”, 2014.07.
7. Takahiro Suzuki, Koichi Ojima, Mai-Khoi Q. Do, Minako Hara, Wataru Mizunoya, Mako Nakamura, Yoshihide Ikeuchi, Judy E. Andeson, Ryuichi Tatsumi, Semaphorin 3A secreted from myogenic stem cells promotes slow-twitch muscle fiber generation, 2013 EMBO Workshop on“Semaphorin Function and Mechanism in Action”, 2013.10, Semaphorin 3A (Sema3A), a class 3 vertebrate-secreted semaphorin originally characterized as a potent neural chemorepellent, is now recognized to play crucial roles in angiogenesis, organogenesis, osteoclastogenesis and immune responses as a multi-functional modulator. Recently, we found that resident myogenic stem cells, satellite cells, up-regulate Sema3A expression and secretion exclusively at the early-myogenic differentiation phase in response to in vivo crush injury and hepatocyte growth factor treatment in the primary cultures (Tatsumi et al., 2009); however, its physiological significance in muscle regeneration is still unknown. Here we show that Sema3A impacts slow-type myosin heavy chain (slow-MyHC) expression in mouse satellite cell cultures. Sema3A-siRNA transfection significantly reduced expression of slow-MyHC as well as the muscle-specific transcription factor myogenin, and the down-stream mediators MEF2 as revealed by qPCR and western blotting analyses. Total MyHC expression level was unchanged, likely due to compensatory up-regulation of fast-MyHC during the 72-hr transfection period. Similar responses (except for fast-MyHC) were also observed in myogenin-knockdown cultures. In addition, reduced myogenin expression induced by immunoneutralization of the receptor neuropilin1 (Npn1) was rescued by co-addition of Sema3A protein. These results therefore indicate that Sema3A may activate a slow-MyHC expression-signaling axis consisting of Npn1, myogenin and MEF2. This model is supported by our comparative observations that satellite cells from soleus muscle (abundant in slow fibers) showed higher expression of Sema3A, myogenin and a co-receptor plexinA2 than those from EDL (Suzuki et al. 2013). Overall, the findings highlight a heretofore unexplored and active role for satellite cell-derived Sema3A as a key modulator of slow fiber generation during muscle regeneration, and advance our understanding of the multi-functional contributions of Sema3A..
8. Ryuichi Tatsumi, Judy E. Andeson, Ronald E. Allen, Muscle regeneration dynamics mediated by resident myogenic stem cells: a possible implication in moto-neuritogenesis and fiber-type regulation, Tucson Symposium 2013 on "The Biology of Muscle Growth and Repair", 2013.09, Skeletal muscle regeneration and work-induced hypertrophy are initiated by mechanical insult or other perturbation and one of the earliest events is triggering the activation (re-entry to cell cycle from G0) of quiescent resident myogenic stem cells, satellite cells. Recent studies of satellite cells in culture and in vivo addressed the possible dual-roles of hepatocyte growth factor (HGF) in the stretch-induced activation and the re-establishing quiescence. In the proposed scenario, the time-coordinated increase in extracellular HGF is a key modulator for the two contrary pathways having low and high thresholds to impact activation and the counterpart quiescence of satellite cells, respectively. Moreover, the role of HGF in muscle repair may not be restricted to myogenesis; we demonstrated that HGF up-regulates expression of secreted axon-guidance molecule semaphorin 3A (Sema3A) in satellite cells at early-differentiation phase in primary cultures and in vivo. The results encourage a possible implication of satellite cells in the spatiotemporal regulation of extracellular Sema3A concentrations, which potentially mediates restoration or remodeling of nerve-muscle connections in muscle regeneration in synchrony with recovery of muscle-fiber integrity and types (fast and slow). Very recently, we found in satellite cell cultures that the Sema3A ligand impacts slow-twitch fiber generation through a muscle-specific transcription factor myogenin-dependent pathway; Sema3A-siRNA transfection significantly reduced expression of slow-type myosin heavy chain (slow-MyHC) as well as myogenin and its co-mediator MEF2. Total MyHC protein expression level was likely unchanged, due to compensatory up-regulation of fast-MyHC and similar responses (except for fast-MyHC) were also observed in myogenin-knockdown cultures. Overall our results highlight the “programmed mechano-biology dynamics” that successful muscle regeneration, comprised of satellite cell-driving myogenesis, intramuscular moto-neuritogenesis and fiber-type regulation (survival), may be a programmed sequence of events that respond to a mechanical perturbation in a synchronous, HGF-dependent and time-coordinated manner..
9. Muscle regeneration dynamics mediated by resident myogenic stem cells
Authored by Ryuichi Tatsumi, Kyushu Univ., Fukuoka, JAPAN

Skeletal muscle regeneration and work-induced hypertrophy are initiated by mechanical insult or other perturbation and one of the earliest events is triggering the activation (re-entry to cell cycle from G0) of quiescent resident myogenic stem cells, satellite cells. Recent studies of satellite cells in culture and in vivo addressed the possible dual-roles of hepatocyte growth factor (HGF) in the stretch-induced activation and the re-establishing quiescence. In the proposed scenario, the time-coordinated increase in extracellular HGF is a key modulator for the two contrary pathways having low and high thresholds to impact activation and the counterpart quiescence of satellite cells, respectively. Moreover, the role of HGF in muscle repair may not be restricted to myogenesis; we demonstrated that HGF up-regulates expression of secreted axon-guidance molecule semaphorin 3A (Sema3A) in satellite cells at early-differentiation phase in primary cultures and in vivo. The results encourage a possible implication of satellite cells in the spatiotemporal regulation of extracellular Sema3A concentrations, which potentially mediates restoration or remodeling of nerve-muscle connections in muscle regeneration in synchrony with recovery of muscle-fiber integrity and types (fast and slow). Overall our results highlight the “programmed mechano-biology dynamics” that successful muscle regeneration, comprised of satellite cell-driving myogenesis and intramuscular moto-neuritogenesis, may be a programmed sequence of events that respond to a mechanical perturbation in a synchronous, HGF-dependent and time-coordinated manner..
10. Programmed mechano-biology of resident myogenic stem cells
Authored by Ryuichi Tatsumi, Kyushu Univ., Fukuoka, JAPAN

Skeletal muscle regeneration and work-induced hypertrophy are initiated by mechanical insult or other perturbation and one of the earliest events is triggering the activation (re-entry to cell cycle from G0) of quiescent resident myogenic stem cells, satellite cells. Recent studies of satellite cells in culture and in vivo addressed the possible dual-roles of hepatocyte growth factor (HGF) in the stretch-induced activation and the re-establishing quiescence. In the proposed scenario, the time-coordinated increase in extracellular HGF is a key modulator for the two contrary pathways having low and high thresholds to impact activation and the counterpart quiescence of satellite cells, respectively. Moreover, the role of HGF in muscle repair may not be restricted to myogenesis; we demonstrated that HGF up-regulates expression of secreted axon-guidance molecule semaphorin 3A (Sema3A) in satellite cells at early-differentiation phase in primary cultures and in vivo. The results encourage a possible implication of satellite cells in the spatiotemporal regulation of extracellular Sema3A concentrations, which potentially mediates restoration or remodeling of nerve-muscle connections in muscle regeneration in synchrony with recovery of muscle-fiber integrity. Overall our results highlight the “programmed mechano-biology” that successful muscle regeneration, comprised of satellite cell-driving myogenesis and intramuscular moto-neuritogenesis, may be a programmed sequence of events that respond to a mechanical perturbation in a synchronous, HGF-dependent and time-coordinated manner..
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14. Do, Mai-Khoi Q., Sato, Y., Sankoda, Y., Shimizu, N., Suzuki, T., Mizunoya, W., Nakamura, M., Ikeuchi, Y., Judy E. Anderson, Ronald E. Allen (2011) Possible implication of myogenic stem cells in regenerative motoneuritogenesis through axon guidance molecule Sema3A expression and secretion, Group Meeting 2011 on Translational Research for Muscular Dystrophy (Dec. 1-2, 2011, Tokyo).
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15. Tatsumi, R. (2011) Possible implication of myogenic stem cells in regenerative motoneuritogenesis, The 26th Annual Research Meeting of the Japanese Orthopaedic Association (Oct. 20, 21th, 2011, Maebashi, Gunma)..
16. Ryuichi Tatsumi, Mechanobiology on muscle hypertrophy and regeneration: HGF/NO-dependent cascade model of satellite cell activation and quiescence mechanism. Lecture at the Graduate School of Veterinary Science, Hokkaido University, Feb. 1st., 2007..
17. Tatsumi R. (2006) Mechanobiology of Skeletal Muscle Satellite Cells., the 10th Annual Symposium on Animal Life Sciences., invited talk.
18. Tatsumi R. (2006) Myostatin Expression in Myogenic Stem cells., Symposium of the 106th Annual Meeting of Japan Society of Animal Science., invited talk.
19. Okamoto, S., Wakamatsu, J.-I., Mizunoya, W., Waga, T., Tatsumi, R., Ikeuchi, Y. (2006) Effects of Apple-Polyphenol Intake on Rat Skeletal Muscle and Lipid Metabolism., the 106th Annual Meeting of Japan Society of Animal Science..
20. Ryuichi Tatsumi, Keitaro Yamanouchi, Toru Hosoyama, Sei-ichi Shiratsuchi, Michiko Yamada, Jun-Ichiro Wakamatsu, Wataru Mizunoya, Yoshihide Ikeuchi, and Ronald E. Allen, A Possible Programmed Mechanism of Muscle Satellite Cell Quiescence: The cell Activator HGF Induces Myostatin Expression and Secretion., FASEB Summer Research Conference 2005, 4rd International Conference on Skeletal Muscle & Stem Cells, Omni Tucson Golf Resort & Spa, Tucson, AZ, US (June 11-16, 2005).
21. Tatsumi, R., Ikeuchi, Y. (2005) More Shine to Meat Production: A Programmed Cascade Model for Muscle Satellite Cell Activation and Quiescence., the Annual Spring Meeting 2005 of Japanese Society for Animal Nutrition and Metabolism..
22. Tatsumi, R., Yamanouchi, K., Hosoyama, T., Ikeuchi, Y. (2005) Activation Factor HGF Induces Satellite Cell Quiescence In Vitro., the 104th Annual Meeting of Japan Society of Animal Science..
23. Tatsumi, R., Ikeuchi, Y., and Hattori, A. (2004) Molecular Mechanism of Muscle Satellite Cell Activation: Mechanical Perturbation triggers Nitric Oxide-Dependent Cascade., the 137th Annual Meeting of Japanese Society of Veterinary Science..
24. Ryuichi Tatsumi and Ronald E. Allen, Satellite Cell Activation in Response to Muscle Stretch and Damage., FASEB Summer Research Conference 2003, 3rd International Conference on Muscle Satellite & Stem Cells, Omni Tucson Golf Resort & Spa, Tucson, AZ, US (July 26-30, 2003), invited speak..
25. Ronald E. Allen and Ryuichi Tatsumi, Satellite Cell Activation in Response to Muscle Damage., Molecular Biology of Muscle Development and Regeneration,
The Banff Centre, Alberta, Canada (May 30-June 4, 2003), invited speak..
26. Takehiro Ogawa, Toshiya Hayashi, Kazumasa Nodake, Shohei Shiraishi, Sunao Mori, Ryuichi Tatsumi,, Yoshihide Ikeuchi and Tatsumi Ito, A Novel Muscle Cell Growth Factor, S-Myotrophin, Promotes the Expression of Fast Myosin in Myotubes Developed from C2C12 Cells., 48th International Congress of Meat Science and Technology, Rome, Italy (August 25-30, 2002)..
27. Ryuichi Tatsumi, Tomowa Sakata, Shannon M. Sheehan, Akihito Hattori and Ronald E. Allen, Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells: the Possible Role of HGF in the Mechanism., FASEB Summer Research Conference 2000, 2nd International Conference on Muscle Satellite & Stem Cells,
Omni Tucson Golf Resort & Spa, Tucson, AZ, US (July 14-19, 2001)..
28. Ryuichi Tatsumi, Shannon M. Sheehan, Hiroyuki Iwasaki, Akihito Hattori and Ronald E. Allen, Mechanical Stretch Induces Activation of Skeletal Muscle Satellite Cells In Vitro., 2000 Keystone Symposia on the Molecular Biology of Muscle Development and Disease, Asilomar, CA, US (May 21-26, 2000)..
29. Yukiko Ito, Ryuichi Tatsumi, Takanori Nishimura and Akihito Hattori,
Solubilization of Myofibrillar Proteins of Chicken Skeletal Muscle in Water., 45th International Congress of Meat Science and Technology, Yokohama, Japan (August 1-6, 1999)..
30. Ryuichi Tatsumi, Kenji Maeda and Koui Takahashi, (1999) Calcium-Induced Splitting of Connectin/Titin Filaments: Localization and Characterization of Calcium-Binding Sites., 45th International Congress of Meat Science and Technology, Yokohama, Japan (August 1-6, 1999)..
31. Ronald. E. Allen and Ryuichi Tatsumi, Satellite Cell Activation and the Role of Hepatocyte Growth Factor/Scatter Factor., Post-natal Myogenesis: Satellite Cells in Action, Boston, US (August 13-16, 1998)., invited speak..
32. Ronald. E. Allen, Ryuichi Tatsumi, and Shannon M. Sheehan, HGF is the Activating Factor in Crushed Muscle Extract and Is an Autocrine Growth Factor for Satellite Cells., 1997 Keystone Symposia on Molecular and Cellular Biology, Molecular Biology of Muscle Development, Aspen, CO, US (April 1-6, 1997)..
Membership in Academic Society
  • Warm Regional Society of Animal Science, Japan
  • Japan Muscle Society (JMS)
  • Japanese Society of Animal Science (JSAS)
  • West Japan Society of Animal Science(WJSAS)
  • Japan Society for Meat Science and Technology (JSMST)
  • Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA)
  • West Japan Society for Bioscience, Biotechnology, and Agrochemistry (WJSBBA)
  • Japanese Society for Animal Nutrition and Metabolism
  • The American Society for Cell Biology (ASCB)
  • The American Physiological Society (APS)
Awards
  • ASJ Excellent Paper Award 2013
    Tatsumi, R.
    Mechano-Biology of Skeletal Muscle Hypertrophy and Regeneration: Possible Mechanism of Stretch-Induced Activation of Resident Myogenic Stem Cells.
    Animal Science Journal 81, 11-20 (2010), Invited Review Article
  • ASJ Excellent Paper Award 2011
    Tatsumi, R. and Allen, R. E.
    Mechano-Biology of Resident Myogenic Stem Cells: Molecular Mechanism of Stretch-Induced Activation of Satellite Cells.
    Animal Science Journal 79, 279-290 (2008), Invited Review Article
  • BBB Excellent Paper Award 2009
    Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., Buchman, V. L., and Ikeuchi, Y.
    Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy.
    Bioscience, Biotechnology and Biochemistry 73, 1748-1756 (2009).
  • R. Tatsumi (2008) Award presented by Japanese Society of Animal Science,
    Research Titile: Mechano-biology on the postnatal muscle hypertrophy and regeneration, March 2008.
Educational
Educational Activities
1. Laboratory Exercise of Basic Chemistry (for undergraduate students)
2. Laboratory Exercise in Animal Chemistry (for undergraduate students)
3. Amimal Biochemistry (for undergraduate students)
4. Basic Animal Science (for undergraduate students)
5. Scientific English (for undergraduate students)
Other Educational Activities
  • 2018.06, Competitive Research Grant of Academic Challenge 2010 from Kyushu University Venture Business Laboratory, “Slow-myofiber commitment by myogenic stem cell-secreted Sema3A and the dietary regulation”; student name: Y. Matsuyoshi (Master Course)..
  • 2011.04.
  • 2010.04.
  • 2010.09, Competitive Research Grant 2010 from Kyushu University Foundation to support student research activity, “Cross-talk between myogenic stem cells and macrophages during muscle hypertrophy and regeneration”; student name: J.-I. Syono (master course)..
  • 2010.08, Grant in Aid 2010-2011 for Research Activity Start-Up from Japan Society for the Promotion of Science (JSPS, No. 22880025), Y.Sato, Research Fellow (post-doctoral)..
  • 2010.06, Competitive Research Grant of Academic Challenge 2010 from Kyushu University Venture Business Laboratory, “Evaluation of calcium ion influx mechanism in satellite cell activation cascade”; student name: M. Hara (master course)..
  • 2010.04, Competitive Research Grant 2010 from Kyushu University Foundation to support student research activity, “Regulation of postnatal motoneuritogenesis by myogenic stem cells”; student name: T. Suzuki (master course)..
  • 2009.05.
  • 2009.04.
  • 2009.04.
  • 2008.07.
  • 2008.04.
  • 2008.04.
  • 2008.04, Competitive Research Grant 2008 from Kyushu University Foundation to support student research activity, “Role of myogenic stem cells in postnatal motor neuron network formation”; student name: Y. Sankoda (master course)..
  • 2006.03, Kyushu University Foundation Grant 2006 to aid international congress fee, “Mechanical stretch-induced activation of skeletal muscle satellite cells requires matrix metalloproteinase (MMP) activity”; student name: M.Yamada (master course)..
  • 2006.04.
  • 2007.04.
  • 2007.09.
  • 2007.05.
  • 2006.03.
  • 2005.09.
Social
Professional and Outreach Activities
Research Collaboration with
1. Ito-hamu Co. (1999, 2000, 2001)
2. Meiji Kenko-hamu Co. (2000, 2001)
3. Katayama Co. (2001)
4. Asahi Beer Co. (2005, 2006).