| 1. |
Yuka Kasahara, Hideyuki Nakashima, Kinichi Nakashima, Seizure-induced hilar ectopic granule cells in the adult dentate gyrus, 10.3389/fnins.2023.1150283, 2023.03. |
| 2. |
Taito Matsuda
Kinichi Nakashima, Natural and forced neurogenesis in the adult brain: Mechanisms and their possible application to treat neurological disorders, Neurosci Res, 10.1016/j.neures.2020.05.011, 2021.05, Neural stem cells (NSCs) in the adult hippocampus generate new neurons via a process referred to as neurogenesis, supporting cognitive functions. Since altered neurogenesis has been reportedly associated with several diseases such as epilepsy, the molecular basis of NSC activity is an important focus in the study of neurogenesis. Furthermore, facilitation of neurogenesis in the injured brain would be an ideal approach to replenish lost neurons for damage recovery. However, natural neurogenesis by endogenous NSCs in the adult brain is insufficient for complete recovery after severe injury. Recent advances in understanding forced neurogenesis from brain-resident non-neuronal cells by direct reprogramming and clearing hurdles to achieve it have improved the ability to replace damaged neurons in the brain. In this review, we describe molecular mechanisms underlying natural and forced neurogenesis, and discuss future directions for treatments of diseases in the central nervous system.. |
| 3. |
Shuzo Matsubara, Taito Matsuda, Kinichi Nakashima, Regulation of Adult Mammalian Neural Stem Cells and Neurogenesis by Cell Extrinsic and Intrinsic Factors, Cells, 10.3390/cells10051145, 2021.05, https://hyoka-lab.ir.kyushu-u.ac.jp/search/FSIServ. |
| 4. |
Tetsuro Yasui, Kinichi Nakashima, Hypoxia epigenetically bestows astrocytic differentiation potential on human pluripotent cell-derived neural stem/precursor cells, Folia Pharmacologica Japonica, 10.1254/fpj.153.54, 2019.01, The central nervous system (CNS) is composed of three major cell types, neurons, astrocytes, and oligodendrocytes, which differentiate from common multipotent neural stem/precursor cells (NS/PCs). However, NS/PCs do not have this multipotentiality from the beginning: neurons are generated first and astrocytes are later during CNS development. This developmental progression is observed in vitro by using human (h) NS/PCs derived from pluripotent cells, such as embryonic- and induced pluripotent-stem cells (ES/ iPSCs), however, in contrast to rodent’s pluripotent cells, they require quite long time to obtain astrocytic differentiation potential. Here, we show that hypoxia confers astrocytic differentiation potential on hNS/PCs through epigenetic alteration for gene regulation. Furthermore, we found that these molecular mechanisms can be applied to functional analysis of patient’ iPSC-derived astrocytes. In this review, we summarize recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NS/PC fate and the development of potential therapeutic strategies for treating astrocyte-mediated neurological disorders.. |
| 5. |
低用量ペルメトリン早期慢性暴露によるマウス次世代雄個体行動影響. |
| 6. |
子どもへの低用量化学物質暴露が誘発する情動認知行動影響とその評価系の開発 幼若期ネオニコチノイド投与が成体マウス脳トランスクリプトームに及ぼす影響. |
| 7. |
子どもへの低用量化学物質暴露が誘発する情動認知行動影響とその評価系の開発 幼若期ネオニコチノイド投与が成体マウス脳トランスクリプトームに及ぼす影響. |
| 8. |
Tomonori Kameda, Takuya Imamura, Kinichi Nakashima, Epigenetic regulation of neural stem cell differentiation towards spinal cord regeneration, Cell and Tissue Research, 10.1007/s00441-017-2656-2, 2018.01, Severe spinal cord injury (SCI) leads to almost complete neural cell loss at the injured site, causing the irreversible disruption of neuronal circuits. The transplantation of neural stem or precursor cells (NS/PCs) has been regarded as potentially effective for SCI treatment because NS/PCs can compensate for the injured sites by differentiating into neurons and glial cells (astrocytes and oligodendrocytes). An understanding of the molecular mechanisms that regulate the proliferation, fate specification and maturation of NS/PCs and their progeny would facilitate the establishment of better therapeutic strategies for regeneration after SCI. In recent years, several studies of SCI animal models have demonstrated that the modulation of specific epigenetic marks by histone modifiers and non-coding RNAs directs the setting of favorable cellular environments that promote the neuronal differentiation of NS/PCs and/or the elongation of the axons of the surviving neurons at the injured sites. In this review, we provide an overview of recent progress in the epigenetic regulation/manipulation of neural cells for the treatment of SCI.. |
| 9. |
Yicheng Zhu, Naohiro Uezono, Tetsuro Yasui, Kinichi Nakashima, Neural stem cell therapy aiming at better functional recovery after spinal cord injury, Developmental Dynamics, 10.1002/dvdy.24558, 2018.01, Injury to the spinal cord causes transection of axon fibers and neural cell death, resulting in disruption of the neural network and severe functional loss. Reconstruction of the damaged neural circuits was once considered to be hopeless as the adult mammalian central nervous system has very poor ability to regenerate. For this reason, there is currently no effective therapeutic treatment for spinal cord injury (SCI). However, with recent developments in stem cell research and cell culture technology, regenerative therapy using neural stem cell (NSC) transplantation has rapidly been developed, and this therapeutic strategy makes it possible to rebuild the destroyed neural circuits. In this review, we discuss the recent breakthroughs in NSC transplantation therapy for SCI. Developmental Dynamics 247:75–84, 2018.. |
| 10. |
Yoichiro Kawamura, Jun Takouda, Koji Yoshimoto, Kinichi Nakashima, New aspects of glioblastoma multiforme revealed by similarities between neural and glioblastoma stem cells, Cell Biology and Toxicology, 10.1007/s10565-017-9420-y, 2018.01, Neural stem cells (NSCs) undergo self-renewal and generate neurons and glial cells under the influence of specific signals from surrounding environments. Glioblastoma multiforme (GBM) is a highly lethal brain tumor arising from NSCs or glial precursor cells owing to dysregulation of transcriptional and epigenetic networks that control self-renewal and differentiation of NSCs. Highly tumorigenic glioblastoma stem cells (GSCs) constitute a small subpopulation of GBM cells, which share several characteristic similarities with NSCs. GSCs exist atop a stem cell hierarchy and generate heterogeneous populations that participate in tumor propagation, drug resistance, and relapse. During multimodal treatment, GSCs de-differentiate and convert into cells with malignant characteristics, and thus play critical roles in tumor propagation. In contrast, differentiation therapy that induces GBM cells or GSCs to differentiate into a neuronal or glial lineage is expected to inhibit their proliferation. Since stem cell differentiation is specified by the cells’ epigenetic status, understanding their stemness and the epigenomic situation in the ancestor, NSCs, is important and expected to be helpful for developing treatment modalities for GBM. Here, we review the current findings regarding the epigenetic regulatory mechanisms of NSC fate in the developing brain, as well as those of GBM and GSCs. Furthermore, considering the similarities between NSCs and GSCs, we also discuss potential new strategies for GBM treatment.. |
| 11. |
Hamazaki, N.
Nakashima, K.
Imamura, T., Manipulation of Promoter-Associated Noncoding RNAs in Mouse Early Embryos for Controlling Sequence-Specific Epigenetic Status, Methods Mol Biol, 10.1007/978-1-4939-6716-2_16, 2017.04, In mammals, transcription in the zygote begins after fertilization. This transcriptional wave is called zygotic gene activation (ZGA). During ZGA, epigenetic modifications, such as DNA methylation and histone modifications, are dynamically and drastically reconstructed in a sequence-specific manner. However, how such orchestrated gene upregulation is regulated remains unknown. Recently, using microinjection techniques, we have revealed that a class of long noncoding RNAs, named promoter-associated noncoding RNAs (pancRNAs), mediates specific gene upregulation through promoter DNA demethylation during ZGA. Here, we describe the experimental methods available to control the expression levels of pancRNAs and to evaluate epigenetic status after pancRNA manipulation.. |
| 12. |
Hamazaki, N.
Nakashima, K.
Hayashi, K.
Imamura, T., Detection of Bidirectional Promoter-Derived lncRNAs from Small-Scale Samples Using Pre-Amplification-Free Directional RNA-seq Method, Methods Mol Biol, 10.1007/978-1-4939-6988-3_6, 2017.04, Development of high-throughput sequencing technologies has uncovered the immensity of the long noncoding RNA (lncRNA) world. Divergently transcribed lncRNAs from bidirectional gene promoters, called promoter-associated noncoding RNAs (pancRNAs), account for ~20% of the total number of lncRNAs, and this major fraction is involved in many biological processes, such as development and cancer formation. Recently, we have found that the pancRNAs activate their partner genes, as represented by the fact that pancIl17d, a pancRNA that is transcribed from the antisense strand of the promoter region of Interleukin 17d (Il17d) at the onset of zygotic gene activation (ZGA), is essential for mouse preimplantation development through Il17d upregulation. The discovery of the expression of a specific set of pancRNAs during ZGA was achieved by using a method that generates directional RNA-seq libraries from small-scale samples. Although there are several methods available for small-scale samples, most of them require a pre-amplification procedure that frequently generates some amplification biases toward a subset of transcripts. We provide here a highly sensitive and reproducible method based on the preparation of directional RNA-seq libraries from as little as 100 mouse oocytes or embryos without pre-amplification for the quantification of lncRNAs as well as mRNAs.. |
| 13. |
Jun Takouda, Sayako Katada, Kinichi Nakashima, Emerging mechanisms underlying astrogenesis in the developing mammalian brain, Proceedings of the Japan Academy Series B: Physical and Biological Sciences, 10.2183/pjab.93.024, 2017.01, In the developing brain, the three major cell types, i.e., neurons, astrocytes and oligodendrocytes, are generated from common multipotent neural stem cells (NSCs). In particular, astrocytes eventually occupy a great fraction of the brain and play pivotal roles in the brain development and functions. However, NSCs cannot produce the three major cell types simultaneously from the beginning; e.g., it is known that neurogenesis precedes astrogenesis during brain development. How is this fate switching achieved? Many studies have revealed that extracellular cues and intracellular programs are involved in the transition of NSC fate specification. The former include growth factor- and cytokine-signaling, and the latter involve epigenetic machinery, including DNA methylation, histone modifications, and non-coding RNAs. Accumulating evidence has identified a complex array of epigenetic modifications that control the timing of astrocytic differentiation of NSCs. In this review, we introduce recent progress in identifying the molecular mechanisms of astrogenesis underlying the tight regulation of neuronal-astrocytic fate switching of NSCs.. |
| 14. |
Naoya Murao, Hirofumi Noguchi, Kinichi Nakashima, Epigenetic regulation of neural stem cell property from embryo to adult, Neuroepigenetics, 10.1016/j.nepig.2016.01.001, Vol.5, pp.1-10, 2016.01, Neural stem cells (NSCs) have the ability to self-renew and give rise to neurons and glial cells (astrocytes and oligodendrocytes) in the mammalian central nervous system. This multipotency is acquired by NSCs during development and is maintained throughout life. Proliferation, fate specification, and maturation of NSCs are regulated by both cell intrinsic and extrinsic factors. Epigenetic modification is a representative intrinsic factor, being involved in many biological aspects of central nervous system development and adult neurogenesis through the regulation of NSC dynamics. In this review, we summarize recent progress in the epigenetic regulation of NSC behavior in the embryonic and adult brain, with particular reference to DNA methylation, histone modification, and noncoding RNAs.. |
| 15. |
Taito Matsuda, Kinichi Nakashima, Bidirectional communication between the innate immune and nervous systems for homeostatic neurogenesis in the adult hippocampus, Neurogenesis, 10.1080/23262133.2015.1081714, 2015.01, A population of proliferating neural stem/progenitor cells located in the subgranular zone of the adult hippocampal dentate gyrus (DG) gives rise to new neurons continuously throughout life, and this process is referred to as adult hippocampal neurogenesis. To date, it has generally been accepted that impairments of adult hippocampal neurogenesis resulting from pathological conditions such as stress, ischemia and epilepsy lead to deficits in hippocampus-dependent learning and memory tasks. Recently, we have discovered that microglia, the major immune cells in the brain, attenuate seizure- induced aberrant hippocampal neurogenesis to withstand cognitive decline and recurrent seizure. In that study, we further showed that Toll-like receptor 9, known as a pathogen-sensing receptor for innate immune system activation, recognizes self-DNA derived from degenerating neurons to induce TNF-a production in the microglia after seizure, resulting in inhibition of seizure-induced aberrant neurogenesis. Our findings provide new evidence that interaction between the innate immune and nervous systems ensures homeostatic neurogenesis in the adult hippocampus and should pave the way for the development of new therapeutic strategies for neurological diseases including epilepsy.. |
| 16. |
Aliya Mari D. Adefuin, Ayaka Kimura, Hirofumi Noguchi, Kinichi Nakashima, Masakazu Namihira, Epigenetic mechanisms regulating differentiation of neural stem/precursor cells, Epigenomics, 10.2217/epi.14.53, 2014.01, Differentiation of neural stem/precursor cells (NS/PCs) into neurons, astrocytes and oligodendrocytes during mammalian brain development is a carefully controlled and timed event. Increasing evidences suggest that epigenetic regulation is necessary to drive this. Here, we provide an overview of the epigenetic mechanisms involved in the developing mammalian embryonic forebrain. Histone methylation is a key factor but other epigenetic factors such as DNA methylation and noncoding RNAs also partake during fate determination. As numerous epigenetic modifications have been identified, future studies on timing and regional specificity of these modifications will further deepen our understanding of how intrinsic and extrinsic mechanisms participate together to precisely control brain development.. |
| 17. |
Takuya Imamura, Masahiro Uesaka, Kinichi Nakashima, Epigenetic setting and reprogramming for neural cell fate determination and differentiation, Philosophical Transactions of the Royal Society B: Biological Sciences, 10.1098/rstb.2013.0511, 2014.01, In the mammalian brain, epigenetic mechanisms are clearly involved in the regulation of self-renewal of neural stem cells and the derivation of their descendants, i.e. neurons, astrocytes and oligodendrocytes, according to the developmental timing and the microenvironment, the 'niche'. Interestingly, local epigenetic changes occur, concomitantly with genome-wide level changes, at a set of gene promoter regions for either down- or upregulation of the gene. In addition, intergenic regions also sensitize the availability of epigenetic modifiers, which affects gene expression through a relatively long-range chromatinic interaction with the transcription regulatory machineries including non-coding RNA (ncRNA) such as promoter-associated ncRNA and enhancer ncRNA. We show that such an epigenetic landscape in a neural cell is statically but flexibly formed together with a variable combination of generally and locally acting nuclear molecules including master transcription factors and cell-cycle regulators. We also discuss the possibility that revealing the epigenetic regulation by the local DNA-RNA-protein assemblies would promote methodological innovations, e.g. neural cell reprogramming, engineering and transplantation, to manipulate neuronal and glial cell fates for the purpose of medical use of these cells.. |
| 18. |
Masakazu Namihira, Kinichi Nakashima, Mechanisms of astrocytogenesis in the mammalian brain, Current Opinion in Neurobiology, 10.1016/j.conb.2013.06.002, 2013.12, In the mammalian central nervous system, astrocytes are the most abundant cell type and play crucial roles in brain development and function. Astrocytes are known to be produced from multipotent neural stem cells (NSCs) at the late gestational stage during brain development, and accumulating evidence indicates that this stage-dependent generation of astrocytes from NSCs is achieved by systematic cooperation between environmental cues and cell-intrinsic programs. Exemplifying the former is cytokine signaling through the gp130-Janus kinase/signal transducer and activator of transcription 3 pathway, and exemplifying the latter is epigenetic modification of astrocyte-specific genes. Here, we introduce recent advances in our understanding of the mechanisms that coordinate astrocytogenesis from NSCs by modulating signaling pathways and epigenetic programs, with a particular focus on the developing mammalian forebrain.. |
| 19. |
Chai MuhChyi, Berry Juliandi, Taito Matsuda, Kinichi Nakashima, Epigenetic regulation of neural stem cell fate during corticogenesis, International Journal of Developmental Neuroscience, 10.1016/j.ijdevneu.2013.02.006, 2013.10, The cerebral cortex comprises over three quarters of the brain, and serves as structural basis for the sophisticated perceptual and cognitive functions. It develops from common multipotent neural stem cells (NSCs) that line the neural tube. Development of the NSCs encompasses sequential phases of progenitor expansion, neurogenesis, and gliogenesis along with the progression of developmental stages. Interestingly, NSCs steadfastly march through all of these phases and give rise to specific neural cell types in a temporally defined and highly predictable manner. Herein, we delineate the intrinsic and extrinsic factors that dictate the progression and tempo of NSC differentiation during cerebral cortex development, and how epigenetic modifications contribute to the dynamic properties of NSCs.. |
| 20. |
妊娠期投与による胎生期バルプロ酸暴露マウスは学習記憶異常と海馬抑制系の減弱を示す. |
| 21. |
齋藤 敦, 落合 希実子, 村上 智彦, 佐野坂 司, 中島 欽一, 和中 明生, 今泉 和則, アストロサイト分化における小胞体ストレス応答の役割(The role of endoplasmic reticulum stress response in astrocyte differentiation), 神経化学, Vol.49, No.2-3, p.494, 2010.08. |
| 22. |
Jun Kanno, Katsuhide Igarashi, Kentaro Tanemura, Hirotugu Asano, Kinichi Nakashima, Glucocorticoid induces expression of astrocyte marker GFAP mRNA in mouse neural stem cells, ENDOCRINE JOURNAL, Vol.57, p.S543, 2010.03. |
| 23. |
脊髄損傷に対するエピジェネティック治療. |
| 24. |
中島 欽一, 神山 淳, 高塚 絵里子, 佐野坂 司, 徳永 暁憲, 岡野 栄之, 神経新生・幹細胞の生物学 REST/NRSFを介した骨形成因子BMPによる新規ニューロン分化抑制機構(A inhibitory mechanism of neuronal differentiation mediated by BMP-induced REST/NRSF), 神経化学, Vol.47, No.2-3, p.215, 2008.08. |
| 25. |
エピジェネティクスにより制御される神経幹細胞運命決定機構. |
| 26. |
ヒストン脱アセチル化酵素阻害剤バルプロ酸による神経幹細胞分化制御機構の解明と損傷脊髄再生治療への応用. |
| 27. |
生命現象との関わり 2.幹細胞分化とエピジェネティクス―神経幹細胞をモデルとして. |
| 28. |
Notchシグナルによる発生段階依存的な神経幹細胞成熟機構の解析. |
| 29. |
メチル化DNA結合タンパク質による神経系細胞分化可塑性制御. |
| 30. |
メチル化DNA結合蛋白質による神経系細胞分化可塑性制御機構の解析. |
| 31. |
レチノイン酸とLIFによる神経幹細胞の相乗的アストロサイト分化誘導. |
| 32. |
Jun Kohyama, Yasushi Kuromi, Masakazu Namihira, Jenny Hsieh, Fred H. Gage, Kinichi Nakashima, DNA methylation regulating neural cell fate specification, CELL STRUCTURE AND FUNCTION, Vol.30, p.3, 2005.06. |
| 33. |
神経幹細胞多分化能獲得機構の解析. |
| 34. |
ハブ毒ホスホリパーゼA2アイソザイムの島内および島間多様性の比較. |
| 35. |
M Namihira, K Nakashima, T Takizawa, T Taga, DNA methylation-mediated regulation of astrocyte differentiation from neural precursor cells in mouse fetal brain, JOURNAL OF NEUROCHEMISTRY, Vol.88, p.31, 2004.02. |
| 36. |
K Shimozaki, M Namihira, K Nakashima, T Taga, Stage- and site-specific DNA demethylation in neural stem cells generated from embryonic stem cells, JOURNAL OF NEUROCHEMISTRY, Vol.88, p.30, 2004.02. |
| 37. |
M Namihira, K Nakashima, T Takizawa, T Taga, DNA methylation-mediated regulation of astrocyte differentiation from neural stem cell in mouse fetal brain, JOURNAL OF NEUROCHEMISTRY, Vol.87, p.165, 2003.12. |
| 38. |
K Shimozaki, M Namihira, K Nakashima, T Taga, Regulation of cell fate-specific DNA methylation in astrocyte differentiation from ES cells, JOURNAL OF NEUROCHEMISTRY, Vol.87, p.165, 2003.12. |
| 39. |
M Takizawa, Nobuhisa, I, K Igarashi, M Ueno, K Nakashima, T Taga, Indispensable role of gp130 signaling in the AGM hematopoiesis., BLOOD, Vol.102, No.11, p.165B, 2003.11. |
| 40. |
Neurogenin1は神経幹細胞においてintegrinα5の発現を抑制する. |
| 41. |
マウスAGM造血期におけるgp130シグナルの役割. |
| 42. |
K Nakashima, T Takizawa, W Ochiai, M Yanagisawa, T Taga, Cytokine-mediated cell fate modulation in the developing brain, JOURNAL OF NEUROCHEMISTRY, Vol.78, p.114, 2001.09. |
| 43. |
日本南西諸島におけるハブ毒腺ホスホリパーゼA2アイソザイムの孤立による進化. |
| 44. |
胎生10.5日マウスdorsal aortaで発現する分泌蛋白と膜蛋白のcDNAクローニング. |
| 45. |
IL‐6ファミリーサイトカインによる胎生期マウス神経上皮細胞のアストロサイトへの分化誘導とその分子機構. |
| 46. |
LIFとBMP2のシグナルクロストークによる未分化神経上皮細胞の分化制御. |
| 47. |
インターロイキンIIにより誘導される未分化神経上皮細胞のアストロサイトへの分化. |
| 48. |
M Narazaki, K Nakashima, T Kishimoto, T Taga, Two distinct pathways that mediate gp130-induced cell proliferation; SHP-2-p42/p44 map kinase pathway and state pathway., TISSUE ANTIGENS, Vol.48, No.4-II, p.CR210, 1996.10. |
| 49. |
Accelerated evolution of viper (Vipera ammodytes Serpentes) subfamily snake venom gland thrombin-like enzyme isoenzyme.. |
| 50. |
Accelerated Evolution of Snake Venom Phospholipase A2 Isozymes to Acquire Multiple Functions.. |
| 51. |
Multiple Functions of Snake Venom Gland phospholipase A2 Isozymes Acquired by Adaptive Evolution: Approach by Protein Engineering.. |
| 52. |
グリーンハブ毒腺塩基性Lys‐49‐ホスホリパーゼA2の精製と一次構造. |
| 53. |
ハブ属異種ヘビ間におけるホスホリパーゼA2アイソザイム遺伝子の比較. |
| 54. |
ヒメハブ毒ホスホリパーゼA2アイソザイムcDNA及び遺伝子のクローニング. |
| 55. |
II型ホスホリパーゼA2の分子進化. |
| 56. |
ハブ毒腺ホスホリパーゼA2アイソザイムの機能の多様性と適応進化. |
| 57. |
ハブ毒ホスホリパーゼA2アイソザイム遺伝子の多様性及び構造解析. |
