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Author Kinichi Nakashima

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Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration.

Takahiro Wakizono, Hideyuki Nakashima, Tetsuro Yasui, Teppei Noda, Kei Aoyagi, Kanako Okada, Yasuhiro Yamada, Takashi Nakagawa, Kinichi Nakashima,

Spiral ganglion neurons (SGNs) are primary auditory neurons in the spiral ganglion that transmit sound information from the inner ear to the brain and play an important role in hearing. Impairment of SGNs causes sensorineural hearing loss (SNHL), and it has been thought until now that SGNs cannot be regenerated ... Read more >>

JCI Insight (JCI insight)
[2021, 6(22):]

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SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia.

Jun Takouda, Sayako Katada, Takuya Imamura, Tsukasa Sanosaka, Kinichi Nakashima,

The brain consists of three major cell types: neurons and two glial cell types (astrocytes and oligodendrocytes). Although they are generated from common multipotent neural stem/precursor cells (NS/PCs), embryonic NS/PCs cannot generate all of the cell types at the beginning of brain development. NS/PCs first undergo extensive self-renewal to expand ... Read more >>

Pharmacol Res Perspect (Pharmacology research & perspectives)
[2021, 9(6):e00749]

Cited: 1 time

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Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development.

Sayako Katada, Jun Takouda, Takumi Nakagawa, Mizuki Honda, Katsuhide Igarashi, Takuya Imamura, Yasuyuki Ohkawa, Shoko Sato, Hitoshi Kurumizaka, Kinichi Nakashima,

During neocortical development, tight regulation of neurogenesis-to-astrogenesis switching of neural precursor cells (NPCs) is critical to generate a balanced number of each neural cell type for proper brain functions. Accumulating evidence indicates that a complex array of epigenetic modifications and the availability of extracellular factors control the timing of neuronal ... Read more >>

Genes Dev (Genes & development)
[2021, 35(21-22):1431-1444]

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Expression level of the reprogramming factor NeuroD1 is critical for neuronal conversion efficiency from different cell types

Kanae Matsuda-Ito, Taito Matsuda, Kinichi Nakashima,

<h4>Summary</h4> Several transcription factors, including NeuroD1, have been shown to act as neuronal reprogramming factors (RFs) that induce neuronal conversion from somatic cells. However, it remains unexplored whether expression levels of RFs in the original cells affect reprogramming efficiency. Here, we show that the neuronal reprogramming efficiency from two distinct ... Read more >>

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Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke

Takashi Irie, Taito Matsuda, Yoshinori Hayashi, Akihide Kamiya, Jun-ichi Kira, Kinichi Nakashima,

Ischaemic brain injury causes permanent neuronal loss, which often results in persistent severe neurological dysfunctions. Although generating new neurons in the injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability. Here, we show that ... Read more >>

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Neuronal activation modulates enhancer activity of genes for excitatory synaptogenesis through de novo DNA methylation.

Tomonori Kameda, Hideyuki Nakashima, Takumi Takizawa, Fumihito Miura, Takashi Ito, Kinichi Nakashima, Takuya Imamura,

Post-mitotic neurons do exhibit DNA methylation changes, contrary to the longstanding belief that the epigenetic pattern in terminally differentiated cells is essentially unchanged. While the mechanism and physiological significance of DNA demethylation in neurons have been extensively elucidated, the occurrence of de novo DNA methylation and its impacts have been ... Read more >>

J Reprod Dev (The Journal of reproduction and development)
[2021, :]

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Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition.

Hiroyoshi Doi, Taito Matsuda, Atsuhiko Sakai, Shuzo Matsubara, Sumio Hoka, Ken Yamaura, Kinichi Nakashima,

Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2021, 118(38):]

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scRNA sequencing uncovers a TCF4-dependent transcription factor network regulating commissure development in mouse.

Marie-Theres Wittmann, Sayako Katada, Elisabeth Sock, Philipp Kirchner, Arif B Ekici, Michael Wegner, Kinichi Nakashima, Dieter Chichung Lie, André Reis,

Transcription factor 4 (TCF4) is a crucial regulator of neurodevelopment and has been linked to the pathogenesis of autism, intellectual disability and schizophrenia. As a class I bHLH transcription factor (TF), it is assumed that TCF4 exerts its neurodevelopmental functions through dimerization with proneural class II bHLH TFs. Here, we ... Read more >>

Development (Development (Cambridge, England))
[2021, 148(14):]

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Transnasal transplantation of human induced pluripotent stem cell-derived microglia to the brain of immunocompetent mice.

Bijay Parajuli, Hiroki Saito, Youichi Shinozaki, Eiji Shigetomi, Hiroto Miwa, Sosuke Yoneda, Miki Tanimura, Shigeki Omachi, Toshiyuki Asaki, Koji Takahashi, Masahide Fujita, Kinichi Nakashima, Schuichi Koizumi,

Microglia are the resident immune cells of the brain, and play essential roles in neuronal development, homeostatic function, and neurodegenerative disease. Human microglia are relatively different from mouse microglia. However, most research on human microglia is performed in vitro, which does not accurately represent microglia characteristics under in vivo conditions. ... Read more >>

Glia (Glia)
[2021, 69(10):2332-2348]

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Generation of ovarian follicles from mouse pluripotent stem cells.

Takashi Yoshino, Takahiro Suzuki, Go Nagamatsu, Haruka Yabukami, Mika Ikegaya, Mami Kishima, Haruka Kita, Takuya Imamura, Kinichi Nakashima, Ryuichi Nishinakamura, Makoto Tachibana, Miki Inoue, Yuichi Shima, Ken-Ichirou Morohashi, Katsuhiko Hayashi,

Oocytes mature in a specialized fluid-filled sac, the ovarian follicle, which provides signals needed for meiosis and germ cell growth. Methods have been developed to generate functional oocytes from pluripotent stem cell-derived primordial germ cell-like cells (PGCLCs) when placed in culture with embryonic ovarian somatic cells. In this study, we ... Read more >>

Science (Science (New York, N.Y.))
[2021, 373(6552):]

Cited: 1 time

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CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis.

Yuta Shirogane, Ryuichi Takemoto, Tateki Suzuki, Tomonori Kameda, Kinichi Nakashima, Takao Hashiguchi, Yusuke Yanagi,

Measles virus (MeV), an enveloped RNA virus in the family <i>Paramyxoviridae</i>, is still an important cause of childhood morbidity and mortality worldwide. MeV usually causes acute febrile illness with skin rash, but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). The disease ... Read more >>

J Virol (Journal of virology)
[2021, 95(14):e0052821]

Cited: 1 time

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Decreased Lamin B1 Levels Affect Gene Positioning and Expression in Postmitotic Neurons.

Azumi Noguchi, Kenji Ito, Yuichi Uosaki, Maky Ideta-Otsuka, Katsuhide Igarashi, Hideyuki Nakashima, Toshikazu Kakizaki, Ruri Kaneda, Hideki Uosaki, Yuchio Yanagawa, Kinichi Nakashima, Hirokazu Arakawa, Takumi Takizawa,

Gene expression programs and concomitant chromatin regulation change dramatically during the maturation of postmitotic neurons. Subnuclear positioning of gene loci is relevant to transcriptional regulation. However, little is known about subnuclear genome positioning in neuronal maturation. Using cultured murine hippocampal neurons, we found genomic locus 14qD2 to be enriched with ... Read more >>

Neurosci Res (Neuroscience research)
[2021, :]

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Regulation of Adult Mammalian Neural Stem Cells and Neurogenesis by Cell Extrinsic and Intrinsic Factors.

Shuzo Matsubara, Taito Matsuda, Kinichi Nakashima,

Tissue-specific stem cells give rise to new functional cells to maintain tissue homeostasis and restore damaged tissue after injury. To ensure proper brain functions in the adult brain, neural stem cells (NSCs) continuously generate newborn neurons that integrate into pre-existing neuronal networks. Proliferation, as well as neurogenesis of NSCs, are ... Read more >>

Cells (Cells)
[2021, 10(5):]

Cited: 1 time

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Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury.

Yicheng Zhu, Naohiro Uezono, Tetsuro Yasui, Masahide Nakajo, Tatsuya Nagai, Dengli Wang, Masahiro Nishibori, Kinichi Nakashima,

Spinal cord injury (SCI) causes motor and sensory deficits and is currently considered an incurable disease. We have previously reported that administration of anti-High Mobility Group Box-1 monoclonal antibody (anti-HMGB1 mAb) preserved lesion area and improved locomotion recovery in mouse model of SCI. In order to further enhance the recovery, ... Read more >>

Neurosci Res (Neuroscience research)
[2021, 172:13-25]

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MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling.

Hideyuki Nakashima, Keita Tsujimura, Koichiro Irie, Takuya Imamura, Cleber A Trujillo, Masataka Ishizu, Masahiro Uesaka, Miao Pan, Hirofumi Noguchi, Kanako Okada, Kei Aoyagi, Tomoko Andoh-Noda, Hideyuki Okano, Alysson R Muotri, Kinichi Nakashima,

Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we ... Read more >>

Cell Rep (Cell reports)
[2021, 35(7):109124]

Cited: 1 time

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Reconstitution of the oocyte transcriptional network with transcription factors.

Nobuhiko Hamazaki, Hirohisa Kyogoku, Hiromitsu Araki, Fumihito Miura, Chisako Horikawa, Norio Hamada, So Shimamoto, Orie Hikabe, Kinichi Nakashima, Tomoya S Kitajima, Takashi Ito, Harry G Leitch, Katsuhiko Hayashi,

During female germline development, oocytes become a highly specialized cell type and form a maternal cytoplasmic store of crucial factors. Oocyte growth is triggered at the transition from primordial to primary follicle and is accompanied by dynamic changes in gene expression<sup>1</sup>, but the gene regulatory network that controls oocyte growth ... Read more >>

Nature (Nature)
[2021, 589(7841):264-269]

Cited: 13 times

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NFκB and TGFβ contribute to the expression of PTPN3 in activated human lymphocytes.

Kazunori Nakayama, Hideya Onishi, Akiko Fujimura, Akira Imaizumi, Makoto Kawamoto, Yasuhiro Oyama, Shu Ichimiya, Satoko Koga, Yuichi Fujimoto, Kinichi Nakashima, Masafumi Nakamura,

We previously reported that protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is upregulated in activated lymphocytes, acts as an immune checkpoint. However, the mechanism by which PTPN3 expression is enhanced in activated lymphocytes is unknown. In this study, we analyzed the mechanism of PTPN3 expression in activated lymphocytes with ... Read more >>

Cell Immunol (Cellular immunology)
[2020, 358:104237]

Cited: 1 time

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Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage.

Akihide Takeuchi, Yuji Takahashi, Kei Iida, Motoyasu Hosokawa, Koichiro Irie, Mikako Ito, J B Brown, Kinji Ohno, Kinichi Nakashima, Masatoshi Hagiwara,

During brain development, neural stem cells (NSCs) initially produce neurons and change their fate to generate glias. While the regulation of neurogenesis is well characterized, specific markers for glial precursor cells (GPCs) and the master regulators for gliogenesis remain unidentified. Accumulating evidence suggests that RNA-binding proteins (RBPs) have significant roles ... Read more >>

Stem Cell Reports (Stem cell reports)
[2020, 15(4):883-897]

Cited: 2 times

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Natural and forced neurogenesis in the adult brain: Mechanisms and their possible application to treat neurological disorders.

Taito Matsuda, Kinichi Nakashima,

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, ... Read more >>

Neurosci Res (Neuroscience research)
[2021, 166:1-11]

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Enhanced processivity of Dnmt1 by monoubiquitinated histone H3.

Yuichi Mishima, Laura Brueckner, Saori Takahashi, Toru Kawakami, Junji Otani, Akira Shinohara, Kohei Takeshita, Ronald Garingalao Garvilles, Mikio Watanabe, Norio Sakai, Hideyuki Takeshima, Charlotte Nachtegael, Atsuya Nishiyama, Makoto Nakanishi, Kyohei Arita, Kinichi Nakashima, Hironobu Hojo, Isao Suetake,

DNA methylation controls gene expression, and once established, DNA methylation patterns are faithfully copied during DNA replication by the maintenance DNA methyltransferase Dnmt1. In vivo, Dnmt1 interacts with Uhrf1, which recognizes hemimethylated CpGs. Recently, we reported that Uhrf1-catalyzed K18- and K23-ubiquitinated histone H3 binds to the N-terminal region (the replication ... Read more >>

Genes Cells (Genes to cells : devoted to molecular & cellular mechanisms)
[2020, 25(1):22-32]

Cited: 3 times

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Early-life exposure to low levels of permethrin exerts impairments in learning and memory with the effects on neuronal and glial population in adult male mice.

Hirokatsu Saito, Kenshiro Hara, Takashi Tominaga, Kinichi Nakashima, Kentaro Tanemura,

Permethrin, a pyrethroid chemical, is widely used as a pesticide because of its rapid insecticidal activity. Although permethrin is considered to exert very low toxicity in mammals, the effects of early, low-level, chronic exposure on the adult central nervous system are unclear. In this study, we investigated the effects of ... Read more >>

J Appl Toxicol (Journal of applied toxicology : JAT)
[2019, 39(12):1651-1662]

Cited: 2 times

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Suppressor of fused controls perinatal expansion and quiescence of future dentate adult neural stem cells.

Hirofumi Noguchi, Jesse Garcia Castillo, Kinichi Nakashima, Samuel J Pleasure,

Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. However, establishment and maintenance of quiescent NSC pools during development is not understood. Here, we show that Suppressor of Fused (Sufu) controls establishment of the quiescent NSC pool during mouse dentate gyrus (DG) development by regulating ... Read more >>

Elife (eLife)
[2019, 8:]

Cited: 5 times

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[Hypoxia epigenetically bestows astrocytic differentiation potential on human pluripotent cell-derived neural stem/precursor cells].

Tetsuro Yasui, Kinichi Nakashima,

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 ... Read more >>

Nihon Yakurigaku Zasshi (Nihon yakurigaku zasshi. Folia pharmacologica Japonica)
[2019, 153(2):54-60]

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Pioneer Factor NeuroD1 Rearranges Transcriptional and Epigenetic Profiles to Execute Microglia-Neuron Conversion.

Taito Matsuda, Takashi Irie, Shutaro Katsurabayashi, Yoshinori Hayashi, Tatsuya Nagai, Nobuhiko Hamazaki, Aliya Mari D Adefuin, Fumihito Miura, Takashi Ito, Hiroshi Kimura, Katsuhiko Shirahige, Tadayuki Takeda, Katsunori Iwasaki, Takuya Imamura, Kinichi Nakashima,

Minimal sets of transcription factors can directly reprogram somatic cells into neurons. However, epigenetic remodeling during neuronal reprogramming has not been well reconciled with transcriptional regulation. Here we show that NeuroD1 achieves direct neuronal conversion from mouse microglia both in vitro and in vivo. Exogenous NeuroD1 initially occupies closed chromatin regions associated ... Read more >>

Neuron (Neuron)
[2019, 101(3):472-485.e7]

Cited: 34 times

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Nox4 Promotes Neural Stem/Precursor Cell Proliferation and Neurogenesis in the Hippocampus and Restores Memory Function Following Trimethyltin-Induced Injury.

Yoji Yoshikawa, Tetsuro Ago, Junya Kuroda, Yoshinobu Wakisaka, Masaki Tachibana, Motohiro Komori, Tomoya Shibahara, Hideyuki Nakashima, Kinichi Nakashima, Takanari Kitazono,

Reactive oxygen species (ROS) modulate the growth of neural stem/precursor cells (NS/PCs) and participate in hippocampus-associated learning and memory. However, the origin of these regulatory ROS in NS/PCs is not fully understood. In the present study, we found that Nox4, a ROS-producing NADPH oxidase family protein, is expressed in primary ... Read more >>

Neuroscience (Neuroscience)
[2019, 398:193-205]

Cited: 4 times

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