Updated on 2026/05/18

Information

 

写真a

 
HOSOKAWA KENTARO
 
Organization
Faculty of Medical Sciences Department of Stem Cell Biology and Medicine Lecturer
Graduate School of Medical Sciences Department of Medical Sciences（Concurrent）
Graduate School of Medical Sciences Department of Medicine（Concurrent）
School of Medicine Department of Medicine（Concurrent）
Title
Lecturer
Profile
Our research focuses on uncovering the fundamental mechanisms that govern hematopoietic tissue — the system responsible for generating blood cells throughout life. We are particularly interested in hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) residing in the bone marrow, and how these cells maintain and renew themselves over time. We take a multifaceted approach to our research. Alongside established techniques in cell biology and histology, we actively incorporate data science methodologies to capture the complexity of biological phenomena from multiple angles. In the lab, we work as a unified team, with members ranging from undergraduate to doctoral students. We are committed to supporting each individual's growth and fostering an environment where curiosity and collaboration drive discovery.
Homepage
External link

Research Areas

  • Life Science / Hematology and medical oncology

Research Interests・Research Keywords

  • Research theme： Analysis of signal networks in hematopoietic microenvironment

    Keyword： Niche, Hematopoietic stem cell, Mesenchymal stem cell

    Research period： 2020.6 - 2026.3

  • Research theme： Functional analysis of telomere binding proteins for self-renewal mechanism of bone marrow hematopoietic stem cells

    Keyword： hematopoietic stem cell, telomere binding protein, energy metabolism

    Research period： 2014.4 - 2027.3

Awards

  • 学術奨励賞

    2019.6   宇部興産学術振興財団   Analysis of normal hematopoiesis and metabolic control mechanism of leukemic stem cells by telomere binding factors

  • 若手特別賞

    2018.10   公益信託 日本白血病研究基金   Functional analysis of telomere binding factors for energy metabolism of leukemic stem cells

  • 奨励賞

    2016.10   日本血液学会   Protection of telomeres 1 (Pot1) regulates hematopoietic stem cell activity during ageing.

    　More details

    Repeated cell divisions induce DNA damage accumulation, which impair stem ce ll function during ageing. However
    the general molecular mechanisms by whic h this occurs remain unclear. Here, we show that expression of
    protection of telomeres 1a (Pot1a), a component of shelterin, is crucial for the preventi on of telomeric
    DNA damage response (DDR) and maintenance of hematopoietic s tem cell (HSC) activity during ageing. We observed
    that HSCs express high le vels of Pot1a during development, yet this expression declines with age. Kno ckdown
    of Pot1a induced an age-related phenotype, marked by increased telome ric DDR, and reduced long-term
    reconstitution activity. In contrast, overexp ression of Pot1a or treatment with exogenous Pot1a protein
    prevented telomer ic DDR, enhanced telomerase activity and rejuvenated HSC activity. Similar r ejuvenation
    was observed upon treatment of human HSCs with recombinant human
    POT1 protein. These results highlight a general, reversible mechanism by wh ich ageing compromises mammalian
    stem cell activity, with widespread implica tions for regenerative medicine.

Papers

  • The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. Reviewed International coauthorship International journal

    Hosokawa Kentaro, MacArthur BD, Ikushima YM, Toyama H, Masuhiro Y, Hanazawa S, Suda T, Fumio Arai

    Nature Communications   8 ( 1 )   2017.10

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-017-00935-4

  • Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. Reviewed

    Hosokawa Kentaro, Fumio Arai, Yoshihara H, Iwasaki H, Nakamura Y, Gomei Y, Suda T

    Blood.   2010.7

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1182/blood-2009-05-224857

  • Cadherin-based adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow. Reviewed International coauthorship

    Hosokawa Kentaro, Fumio Arai, Yoshihara H, Iwasaki H, Hembree M, Yin T, Nakamura Y, Gomei Y, Takubo K, Shiama H, Matsuoka S, Li L, Suda T

    Cell Stem Cell.   2010.3

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stem.2009.04.013.

  • Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction. Reviewed

    Hosokawa Kentaro, Fumio Arai, Yoshihara H, Nakamura Y, Gomei Y, Iwasaki H, Miyamoto K, Shima H, Ito K, Suda T

    Biochem Biophys Res Commun.   2007.11

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2007.09.014.

  • Acute myeloid leukemia stem cells remodel the bone marrow niche via TGF-β-activated Alcam+ bone lining cells, creating a self-sustaining environment Reviewed

    Ngan Thi Kim Nguyen, Hisayuki Yao, Kentaro Hosokawa, Yuki Esaki, Ryosuke Yuta, Shunichi Adachi, Fumio Arai

    Leukemia   39 ( 7 )   1778 - 1782   2025.7   （ ISSN:0887-6924 eISSN:1476-5551 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Leukemia  

    DOI： 10.1038/s41375-025-02640-4

    Web of Science

    Scopus

    PubMed

  • POT1a deficiency in mesenchymal niches perturbs B-lymphopoiesis Reviewed International coauthorship

    Nakashima, K; Kunisaki, Y; Hosokawa, K; Gotoh, K; Yao, H; Yuta, R; Semba, Y; Nogami, J; Kikushige, Y; Stumpf, PS; MacArthur, BD; Kang, D; Akashi, K; Ohga, S; Arai, F

    COMMUNICATIONS BIOLOGY   6 ( 1 )   996   2023.9   （ eISSN:2399-3642 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Communications Biology  

    Protection of telomeres 1a (POT1a) is a telomere binding protein. A decrease of POT1a is related to myeloid-skewed haematopoiesis with ageing, suggesting that protection of telomeres is essential to sustain multi-potency. Since mesenchymal stem cells (MSCs) are a constituent of the hematopoietic niche in bone marrow, their dysfunction is associated with haematopoietic failure. However, the importance of telomere protection in MSCs has yet to be elucidated. Here, we show that genetic deletion of POT1a in MSCs leads to intracellular accumulation of fatty acids and excessive ROS and DNA damage, resulting in impaired osteogenic-differentiation. Furthermore, MSC-specific POT1a deficient mice exhibited skeletal retardation due to reduction of IL-7 producing bone lining osteoblasts. Single-cell gene expression profiling of bone marrow from POT1a deficient mice revealed that B-lymphopoiesis was selectively impaired. These results demonstrate that bone marrow microenvironments composed of POT1a deficient MSCs fail to support B-lymphopoiesis, which may underpin age-related myeloid-bias in haematopoiesis.

    DOI： 10.1038/s42003-023-05374-0

    Web of Science

    Scopus

    PubMed

  • Machine Learning of Hematopoietic Stem Cell Divisions from Paired Daughter Cell Expression Profiles Reveals Effects of Aging on Self-Renewal Reviewed International coauthorship International journal

    Fumio Arai, Patrick S Stumpf, Yoshiko M Ikushima, Kentaro Hosokawa, Aline Roch, Matthias P Lutolf, Toshio Suda, Ben D MacArthur

    CELL SYSTEMS   11 ( 6 )   640 - +   2020.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    Changes in stem cell activity may underpin aging. However, these changes are not completely understood. Here, we combined single-cell profiling with machine learning and in vivo functional studies to explore how hematopoietic stem cell (HSC) divisions patterns evolve with age. We first trained an artificial neural network (ANN) to accurately identify cell types in the hematopoietic hierarchy and predict their age from single-cell gene-expression patterns. We then used this ANN to compare identities of daughter cells immediately after HSC divisions and found that the self-renewal ability of individual HSCs declines with age. Furthermore, while HSC cell divisions are deterministic and intrinsically regulated in young and old age, they are variable and niche sensitive in mid-life. These results indicate that the balance between intrinsic and extrinsic regulation of stem cell activity alters substantially with age and help explain why stem cell numbers increase through life, yet regenerative potency declines.

    DOI： 10.1016/j.cels.2020.11.004

  • Mitochondrial Protein Synthesis Is Essential for Terminal Differentiation of CD45(-) TER119(-) Erythroid and Lymphoid Progenitors Reviewed International journal

    Kazuhito Gotoh, Yuya Kunisaki, Soichi Mizuguchi, Daiki Setoyama, Kentaro Hosokawa, Hisayuki Yao, Yuya Nakashima, Mikako Yagi, Takeshi Uchiumi, Yuichiro Semba, Jumpei Nogami, Koichi Akashi, Fumio Arai, Dongchon Kang

    ISCIENCE   23 ( 11 )   2020.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    p32/C1qbp regulates mitochondrial protein synthesis and is essential for oxidative phosphorylation in mitochondria. Although dysfunction of p32/C1qbp impairs fetal development and immune responses, its role in hematopoietic differentiation remains unclear. Here, we found that mitochondrial dysfunction affected terminal differentiation of newly identified erythroid/B-lymphoid progenitors among CD45- Ter119- CD31- triple-negative cells (TNCs) in bone marrow. Hematopoietic cell-specific genetic deletion of p32/C1qbp (p32cKO) in mice caused anemia and B-lymphopenia without reduction of hematopoietic stem/progenitor cells. In addition, p32cKO mice were susceptible to hematopoietic stress with delayed recovery from anemia. p32/C1qbp-deficient CD51- TNCs exhibited impaired mitochondrial oxidation that consequently led to inactivation of mTORC1 signaling, which is essential for erythropoiesis. These findings uncover the importance of mitochondria, especially at the stage of TNCs during erythropoiesis, suggesting that dysregulation of mitochondrial protein synthesis is a cause of anemia and B-lymphopenia with an unknown pathology.

    DOI： 10.1016/j.isci.2020.101654

  • The role of telomere binding molecules for normal and abnormal hematopoiesis Invited Reviewed

    Kentaro Hosokawa, Fumio Arai

    Int J Hematol .   107 ( 6 )   646 - 655   2018.6

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s12185-018-2432-4.

  • Determining c-Myb protein levels can isolate functional hematopoietic stem cell subtypes Reviewed International coauthorship International journal

    Sakamoto H, Takeda N, Fumio Arai, Hosokawa Kentaro, Garcia P, Suda T, Frampton J, Ogawa M

    Stem Cells   2015.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/stem.1855

  • Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression. Reviewed

    Horio E, Kadomatsu T, Miyata K, Arai Y, Hosokawa Kentaro, Doi Y, Ninomiya T, Horiguchi H, Endo M, Tabata M, Tazume H, Tian Z, Takahashi O, Terada K, Takeya M, Hao H, Hirose N, Minami T, Suda T, Oike Y

    Arterioscler Thromb Vasc Biol.   2014.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1161/ATVBAHA.113.303116

  • Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells. Reviewed

    Yamashita M, Nitta E, Nagamatsu Go, Ikushima YM, Hosokawa Kentaro, Fumio Arai, Suda T

    Biochem Biophys Res Commun.   2013.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2013.10.032.

  • Prostaglandin E(2) regulates murine hematopoietic stem/progenitor cells directly via EP4 receptor and indirectly through mesenchymal progenitor cells. Reviewed

    Ikushima YM, Hosokawa Kentaro, Fumio Arai, Toyama H, Takubo K, Furuyashiki T, Narumiya S, Suda T

    Blood.   2013.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1182/blood-2012-06-437889

  • Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term repopulation ability of hematopoietic stem cells. Reviewed

    Ikushima YM, Fumio Arai, Nakamura Y, Hosokawa Kentaro, Kubota Y, Hirashima M, Toyama H, Suda T

    Biochem Biophys Res Commun.   2013.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2012.11.002

  • N-cadherin+ HSCs in fetal liver exhibit higher long-term bone marrow reconstitution activity than N-cadherin- HSCs. Reviewed

    Toyama H, Fumio Arai, Hosokawa Kentaro, Ikushima YM, Suda T

    Biochem Biophys Res Commun.   2012.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2012.10.058

  • p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. Reviewed

    Zou P, Yoshihara H, Hosokawa Kentaro, Tai I, Shinmyozu K, Tsukahara F, Maru Y, Nakayama K, Keiichi Nakayama, Suda T

    Cell Stem Cell.   2011.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stem.2011.07.003

  • Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism. Reviewed

    Nitta E, Yamashita M, Hosokawa Kentaro, Xian M, Takubo K, Fumio Arai, Nakada S, Suda T

    Blood.   2011.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1182/blood-2010-08-297390

  • Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells. Reviewed

    Nakamura Y, Fumio Arai, Iwasaki H, Hosokawa Kentaro, Kobayashi I, Gomei Y, Matsumoto Y, Yoshihara H, Suda T

    Blood.   2010.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1182/blood-2009-08-239194

  • 骨中コラーゲン高親和性タンパク質の骨芽細胞様細胞株MC3T3-E1細胞の骨形成過程に及ぼす影響. Reviewed

    村上 拡治, @細川 健太郎, 祭 友昭, 笠井 久隆, 井上 順雄

    日本保健科学学会誌   12 ( 4 )   237 - 244   2010.3

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    我々は既に、ウシ大腿骨皮質骨中にコラーゲンに高親和性を持つ、酸性タンパク質を検出、報告した。本研究では、骨芽細胞様細胞株MC3T3-E1細胞の培養系を用いて、このコラーゲン高親和性タンパク質(C-HAP)が骨形成過程に及ぼす影響を検討した。C-HAPを含む内因性のタンパク質精製画分(2画分)と外因性のポリグルタミン酸(PGA)をそれぞれMC3T3-E1細胞の培養系に添加し、細胞形態、ALP活性および骨基質の石灰化を評価した。その結果、(1)PGAはALP活性を増強し、タンパク質の集積と骨基質の石灰化を促進したこと、(2)C-HAPはALP活性を減弱し、タンパク質の集積と骨基質の石灰化を促進したこと、また、(3)PGAが細胞を多角形に保つのに対して、C-HAPは細胞を紡錘形に変えたことが明らかとなった。以上の結果を踏まえて、骨中のコラーゲン高親和性タンパク質の骨形成過程における役割を考察した。

    DOI： 10.24531/jhsaiih.12.4_237

  • Functional differences between two Tie2 ligands, angiopoietin-1 and -2, in regulation of adult bone marrow hematopoietic stem cells. Reviewed

    Gomei Y, Nakamura Y, Yoshihara H, Hosokawa Kentaro, Iwasaki H, Suda T, Fumio Arai

    Exp Hematol.   2010.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.exphem.2009.11.007.

  • Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice. Reviewed

    Shima H, Takubo K, Iwasaki H, Yoshihara H, Gomei Y, Hosokawa Kentaro, Fumio Arai, Takahashi T, Suda T

    Biochem Biophys Res Commun.   2009.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2008.11.056.

  • Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Reviewed

    Matsuoka S, Oike Y, Onoyama I, Iwama A, Fumio Arai, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K, Miyamoto K, Yoshiwara H, Hosokawa Kentaro, Nakamura Y, Gomei Y, Iwasaki H, Hayashi Y, Matsuzaki Y, Keiichi Nakayama, Suda T

    Genes Dev.   2008.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1101/gad.1621808

  • Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Reviewed

    Yoshihara H, Fumio Arai, Hosokawa Kentaro, Hagiwara T, Takubo K, Nakamura Y, Gomei Y, Iwasaki H, Matsuoka S, Miyamoto K, Miyazaki H, Takahashi T, Suda T

    Cell Stem Cell.   2007.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stem.2007.10.020

  • Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Reviewed

    Miyamoto K, Araki KY, Naka K, Fumio Arai, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K, Ohmura M, Chen C, Hosokawa Kentaro, Nakauchi H, Nakayama K, Keiichi Nakayama, Harada M, Motoyama N, Suda T, Hirao A

    Cell Stem Cell.   2007.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stem.2007.02.001

  • Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes. Reviewed

    Ito K, Takubo K, Fumio Arai, Satoh H, Matsuoka S, Ohmura M, Naka K, Azuma M, Miyamoto K, Hosokawa Kentaro, Ikeda Y, Mak TW, Suda T, Hirao A

    J Immunol.   2007.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.4049/jimmunol.178.1.103.

  • Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Reviewed

    Ito K, Hirao A, Fumio Arai, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa Kentaro, Ikeda Y, Suda T

    Nat Med.   2006.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nm1388

  • Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Reviewed International coauthorship

    Ito K, Hirao A, Fumio Arai, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa Kentaro, Sakurada K, Nakagata N, Ikeda Y, Mak TW, Suda T

    Nature.   2004.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature02989

▼display all

Books

  • Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche.

    @Arai F, @Hosokawa K, Toyama H, Matsumoto Y, Suda T.（Role：Joint author）

    Ann N Y Acad Sci.  2012.8 

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    Responsible for pages：1266 (1): 72-77   Language：English   Book type：Scholarly book

    Cell-cell and cell-extracellular matrix interactions between hematopoietic stem cells (HSCs) and their niches are critical for the maintenance of stem cell properties. Here, it is demonstrated that a cell adhesion molecule, N-cadherin, is expressed in hematopoietic stem/progenitor cells (HSPCs) and plays a critical role in the regulation of HSPC engraftment. Furthermore, overexpression of N-cadherin in HSCs promoted quiescence and preserved HSC activity during serial bone marrow (BM) transplantation (BMT). Inhibition of N-cadherin by the transduction of N-cadherin short hairpin (sh) RNA (shN-cad) reduced the lodgment of donor HSCs to the endosteal surface, resulting in a significant reduction in long-term engraftment. shN-cad-transduced cells were maintained in the spleen for six months after BMT, indicating that N-cadherin expression in HSCs is specifically required in the BM. These findings suggest that N-cadherin-mediated cell adhesion is functionally essential for the regulation of HSPC activities in the BM niche.

    DOI： 10.1111/j.1749-6632.2012.06576.x.

  • Network analysis in systems biology. Gene expression profiling and regulatory networks in single cell. Network analysis in systems biology.

    @Arai F, @Hosokawa K, Matsumoto Y, Toyama H, Suda T.（Role：Joint author）

    Springer International Publishing AG.  2012.1 

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    Responsible for pages：pp. 1-13 ISBN 978-94-007-4330-4   Language：English   Book type：Scholarly book

  • Niche regulation of hematopoietic stem cells in the endosteum.

    @Arai F, Yoshihara H, @Hosokawa K, Nakamura Y, Gomei Y, Iwasaki H, Suda T.（Role：Joint author）

    Ann N Y Acad Sci  2009.5 

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    Responsible for pages：1176:36-46   Language：English   Book type：Scholarly book

    During postnatal life, the bone marrow (BM) supports both the self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized niches. The interaction of HSCs with their niches also regulates the quiescence of HSCs. HSC quiescence is critical to ensure lifelong hematopoiesis and to protect the HSC pool from myelotoxic insult and premature exhaustion under conditions of hematopoietic stress. Here we identified long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, Mpl, as a quiescent population in adult BM. THPO was produced by bone-lining cells in the endosteum. Inhibition and stimulation of the THPO/Mpl pathway produced opposite effects on the quiescence of LT-HSC. Exogenous THPO transiently increased the quiescent LT-HSC population, such as side-population and pyronin Y-negative cells. In contrast, administration of an anti-Mpl neutralizing antibody, AMM2, suppressed the quiescence of LT-HSCs and enabled HSC engraftment without irradiation, indicating that inhibition of THPO/Mpl signaling reduces HSC-niche interactions. Moreover, it suggests that inhibiting the HSC-niche interaction could represent a novel technique for bone marrow transplantation without irradiation. Altogether, these data suggest that the THPO/Mpl signaling pathway is a novel niche component in the endosteum, and in the steady-state condition, this signaling pathway plays a critical role in the regulation of LT-HSCs in the osteoblastic niche.

Presentations

  • Function of Foxp2 on the self-renewal ability of hematopoietic stem cells

    @細川 健太郎,@新井 文用

    第84回日本血液学会学術集会  2022.10 

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    Event date： 2022.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：福岡   Country：Japan  

  • Foxp2 is essential for the quiescent state and self-renewal capacity of hematopoietic stem cells. International conference

    @細川 健太郎, #森本 早紀, @國﨑 祐哉, #今西 春香, #上原 康史, @兵田 朋子, @新井 文用

    International Society for Experimental Hematology  2017.8 

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    Event date： 2017.8

    Language：English  

    Venue：Goethe University   Country：Germany  

  • Shelterin component protection of telomeres 1 (Pot1) plays a critical role in the self-renewal of HSCs. International conference

    @細川 健太郎, Benjamin MacArthur, 生島 芳子, 花澤 重正, 須田 年生, @新井 文用

    Joint symposium of PNU and Kyushu Univ  2015.8 

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    Event date： 2015.8

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：九州大学　病院キャンパス   Country：Japan  

  • POT1 regulates self-renewal activity of cord blood hematopoietic stem cells International conference

    @細川 健太郎, 生島 芳子, Benjamin MacArthur, 須田 年生, @新井 文用

    International Society for Experimental Hematology  2014.8 

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    Event date： 2014.8

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：Hyatt Regency Montreal, Montreal   Country：Canada  

    Other Link： https://iseh.site-ym.com/

  • Pot1 regulates hematopoietic stem cell activity during aging

    @細川 健太郎, 生島 芳子, Benjamin MacArthur, 須田 年生, @新井 文用

    幹細胞シンポジウム  2014.5 

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    Event date： 2014.5

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：福岡県　福岡市　九州大学　医学部　百年講堂   Country：Japan  

MISC

  • The role of telomere binding molecules for normal and abnormal hematopoiesis.

    @Hosokawa K, @Arai F.

    Int J Hematol.   2018.5

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1007/s12185-018-2432-4

    Other Link： https://link.springer.com/article/10.1007%2Fs12185-018-2432-4

    Repository Public URL： https://hdl.handle.net/2324/7172610

  • Functional analysis of Protection of Telomeres 1a (Pot1a) in regulation of hematopoietic stem cell aging.

    @細川健太郎, Macarthur Ben D., 生島芳子, 外山弘文, 舛廣善和, 花澤重正, 須田年生, @新井文用

    臨床血液   2017.9

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    Repeated cell divisions induce DNA damage accumulation, which impairs stem cell function during aging. However, the general molecular mechanisms by which this occurs remain unclear. Herein, we show that the expression of protection of telomeres 1a (Pot1a), a component of shelterin, is crucial for prevention of telomeric DNA damage response (DDR) and maintenance of hematopoietic stem cell (HSC) activity during aging. We observed that HSCs express high levels of Pot1a during development, and this expression declines with aging. Knockdown of Pot1a induced an age-related phenotype, characterized by increased telomeric DDR and reduced long-term reconstitution activity. In contrast, treatment with exogenous Pot1a protein prevented telomeric DDR, which decreased stem cell activity and partially rejuvenated HSC activity. These results highlight a general, reversible mechanism by which aging compromises mammalian stem cell activity, with widespread implications for regenerative medicine.

    DOI： 10.11406/rinketsu.58.942

Professional Memberships

  • Stem Cell Research Symposium

  • THE JAPANESE SOCIETY OF HEMATOLOGY

  • International Society for Experimental Hematology

  • American Society of Hematology

Academic Activities

  • ファシリテーター

    第77回日本血液学会学術集会  （ Japan ） 2015.10

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    Type：Competition, symposium, etc. 

Research Projects

  • 内因性カンナビノイドシステムを介した造血幹細胞制御機構の解明

    Grant number：26K11285  2026.4 - 2029.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    細川 健太郎

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    Grant type：Scientific research funding

    CiNii Research

  • Elucidation of the mechanism of hematopoietic stem cell maintenance by newly identified bone marrow mesenchymal stem cells.

    Grant number：23K27626  2024.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    新井 文用, 細川 健太郎, 八尾 尚幸

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    Grant type：Scientific research funding

    骨内膜領域に存在するALCAM+Itga8+ 細胞が多能性と造血支持能を持つMSCであることを見出した。本研究では、新たに同定されたMSCと他のMSC分画との関係性を理解することで、MSCの機能的階層性を明らかにする。また、ALCAM+Itga8+ MSCによるHSCの維持機構を解明する。さらに、転移学習を駆使して、ALCAM+Itga8+ MSCに相当するヒトMSCの同定に挑戦する。本研究の成果は、造血制御機構の解明だけでなく、HSCの機能低下の防止、さらには機能回復にも応用できると考える。また、治療に効果的なMSCを同定することで、移植治療や再生医療の発展に貢献することが期待される。

    CiNii Research

  • 新たに同定した骨髄間葉系幹細胞による造血幹細胞の維持機構の解明

    Grant number：23H02935  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship：Coinvestigator(s)  Grant type：Scientific research funding

  • Function of telomere binding factors in normal and tumor hematopoietic microenvironments

    Grant number：23K07861  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    新井 文用, 細川 健太郎

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    Authorship：Principal investigator  Grant type：Scientific research funding

    本研究では、正常造血や白血病病態におけるニッチ機構の解明を目的とし、テロメア結合因子Pot1の機能を明らかにすることで、AML支持因子の同定を行う。Pot1が転写因子として機能することに着目し、AML支持因子の標的候補を特定することを目的とする。同定された標的に対する阻害剤探索や開発を通じ、AML支持機構の破壊を主軸とした新規治療法の確立に繋がることが期待される。

    CiNii Research

  • Identification of transcriptional signaling networks that control the quality and quantity of the bone marrow microenvironment

    Grant number：20K08733  2020 - 2022

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hosokawa Kentaro

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    Authorship：Principal investigator  Grant type：Scientific research funding

    In this study, we aimed to clarify the function of the forkhead transcription factor Foxp2 on hematopoietic support and self-renewal in bone marrow mesenchymal stem cells (MSCs), and analyzed MSC-specific Foxp2-deficient mice. We found that MSCs exhibit decreased self-renewal capacity and decreased expression of hematopoietic supporting factors. Furthermore, we found that the effects of Foxp2 deficiency on the cell cycle and metabolism of hematopoietic stem cells (HSCs) resulted in a decrease in self-renewal capacity and bone marrow remodeling capacity.

    CiNii Research

  • Elucidating the functional regulation mechanism of the hematopoietic microenvironment (niche) by the shelterin factor

    Grant number：20H03711  2020

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Arai Fumio

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    Authorship：Coinvestigator(s)  Grant type：Scientific research funding

    This study investigated the function and aging regulation of mesenchymal stem cells (MSCs), the primary niche cells of hematopoietic stem cells (HSCs). We focused on the functional role of the shelterin factor POT1a in regulating MSC. MSC function, which declines with aging, is postulated to be involved in the functional decline of HSCs. This study found that POT1a maintains the stem cell activity of MSCs and their capacity to differentiate into osteoblasts and suppresses their functional decline with aging. In addition, the study showed that loss of POT1a reduced the hematopoietic supportive capacity of MSCs and impaired HSC function. These findings suggest that POT1a is essential in maintaining MSCs and their function as niche cells. The results of this study may be a crucial step toward establishing methods for the prevention and treatment of aging-related hematologic diseases.

    CiNii Research

  • 造血幹細胞の未分化性維持に対する転写因子Foxp2の機能解析

    Grant number：17K09907  2017 - 2019

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 次世代型人工ニッチを用いた造血幹細胞の非対称分裂制御機構の解明と体外増幅

    Grant number：17H04208  2017 - 2019

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship：Coinvestigator(s)  Grant type：Scientific research funding

  • シングルセル統合解析による新規間葉系幹細胞の同定と造血制御能の解明

    Grant number：15K15366  2015 - 2016

    Grants-in-Aid for Scientific Research  Grant-in-Aid for challenging Exploratory Research

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • テロメア結合蛋白POT1の増強によるヒト造血幹細胞の体外増幅技術への挑戦

    Grant number：25670453  2013 - 2014

    Grants-in-Aid for Scientific Research  Grant-in-Aid for challenging Exploratory Research

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 造血幹細胞における細胞競合を介した増殖制御機構の解明

    Grant number：24689041  2012 - 2014

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (A)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 造血および白血病幹細胞ニッチの分子機構とその制御

    Grant number：23249053  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

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    Authorship：Coinvestigator(s)  Grant type：Scientific research funding

  • 造血幹細胞の単一細胞単位での非対称分裂機構の解析

    Grant number：22790920  2010 - 2011

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 骨髄内ニッチによる造血幹細胞制御機構の解明

    Grant number：07J02999  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for JSPS Fellows

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 骨髄内ニッチによる造血幹細胞制御機構の解明

    2007 - 2008

    Japan Society for the Promotion of Science  Research Fellowships for Young Scientists

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    Authorship：Principal investigator  Grant type：Joint research

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Educational Activities

  • 1. Initial research support and guidance in the laboratory assignment of a third-year student at Kyushu University School of Medicine or department of life sciences
    2. Support and guidance for graduation research at Kyushu University Graduate School of Medicine, fourth grader
    3. Support and guidance for graduate studies of master's or doctoral students at Kyushu University Graduate School of Medicine