ブレイキングダウンアプリ解約

-->   Kinichi Nakashima Last modified date：2024.05.09 Professor / Stem Cell Biology and Medicine Department of Stem Cell Biology and Medicine Faculty of Medical Sciences 1 Research Interests 2 Academic Activities 2.1 Papers 2.2 Reports 2.3 Presentations E-Mail　*Since the e-mail address is not displayed in Internet Explorer, please use another web browser:Google Chrome, safari. Homepage https://kyushu-u.elsevierpure.com/en/persons/kinichi-nakashima　Reseacher Profiling Tool　Kyushu University Pure Academic Degree PhD Country of degree conferring institution (Overseas) No Field of Specialization Neuroscience, Stem cell biology, Epigenetics Total Priod of education and research career in the foreign country 00years00months Outline Activities Research for verifying mechanisms of neural cell differentiation and their application to regenerative medicine. Research Research Interests Research for verifying mechanisms of neural cell differentiation and their application to regenerative medicinekeyword : Neural Stem Cells, Differentiation, Epigenetics, direct reprogramming2013.04～2028.12. Academic Activities Reports  Show All Reports >> Papers  Show All Papers >> 1. Irie T, Matsuda T, Hayashi Y, Matsuda-Ito K, Kamiya A, Masuda T, Prinz M, Isobe N, Kira JI, Nakashima K., Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke, Proc Natl Acad Sci USA, in press, 2023.10, Although generating new neurons in the ischemic 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 direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischemic brain injury. After transient middle cerebral artery occlusion in adult mice, microglia/macrophages converge at the lesion core of the striatum, where neuronal loss is prominent. Targeted expression of a neurogenic transcription factor, NeuroD1, in microglia/macrophages in the injured striatum enables their conversion into induced neuronal cells that functionally integrate into the existing neuronal circuits. Furthermore, NeuroD1-mediated induced neuronal cell generation significantly improves neurological function in the mouse stroke model, and ablation of these cells abolishes the gained functional recovery. Our findings thus demonstrate that neuronal conversion contributes directly to functional recovery after stroke.. 2. Sayako Katada,Jun Takouda,Takumi Nakagawa,Mizuki Honda,Katsuhide Igarashi, Takuya Imamura,Yasuyuki Ohkawa,Shoko Sato,Hitoshi Kurumizaka,Kinichi Nakashima, Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development, Genes Dev, 10.1101/gad.348797.121., 35, 1431-1444, 2021.11, 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. Accumulatingevidence indicates that a complex array of epigenetic modifications and the availability of extracellular factorscontrol the timing of neuronal and astrocytic differentiation. However, our understanding of NPC fate regulation isstill far from complete. Bone morphogenetic proteins (BMPs) are renowned as cytokines that induce astrogenesis ofgliogenic late-gestational NPCs. They also promote neurogenesis of mid-gestational NPCs, although the underlyingmechanisms remain elusive. By performing multiple genome-wide analyses, we demonstrate that Smads, transcriptionfactors that act downstream from BMP signaling, target dramatically different genomic regions in neurogenicand gliogenic NPCs. We found that histone H3K27 trimethylation and DNA methylation around Smadbindingsites change rapidly as gestation proceeds, strongly associated with the alteration of accessibility of Smads totheir target binding sites. Furthermore, we identified two lineage-specific Smad-interacting partners—Sox11 forneurogenic and Sox8 for astrocytic differentiation—that further ensure Smad-regulated fate-specific gene induction.Our findings illuminate an exquisite regulation of NPC property change mediated by the interplay betweencell-extrinsic cues and -intrinsic epigenetic programs during cortical development.. 3. Doi, H. Matsuda, T. Sakai, A. Matsubara, S. Hoka, S. Yamaura, K. Nakashima, K., Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition, Proc Natl Acad Sci USA, 10.1073/pnas.2107596118, 118, 38, 2021.09, 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 a view for developing a novel immune checkpoint inhibitor that suppresses PTPN3. Through the activation process, lymphocytes showed enhanced NFkappaB activation as well as increased PTPN3 expression. NFkappaB enhanced proliferation, migration, and cytotoxicity of lymphocytes. Furthermore, NFkappaB enhanced PTPN3 expression and tyrosine kinase activation. TGFbeta reduced PTPN3 expression and NFkappaB activation in the cancer microenvironment, and suppressed the biological activity of lymphocytes. The results of this study are expected to provide significant implications for improving existing immunotherapy and developing novel immunotherapy.. 4. Nakashima, H. Tsujimura, K. Irie, K. Imamura, T. Trujillo, C. A. Ishizu, M. Uesaka, M. Pan, M. Noguchi, H. Okada, K. Aoyagi, K. Andoh-Noda, T. Okano, H. Muotri, A. R. Nakashima, K., MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling, Cell Reports, 10.1016/j.celrep.2021.109124, 35, 7, 2021.05, 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 show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.. Presentations  Show All Presentations >> Unauthorized reprint of the contents of this database is prohibited. Copyright © 2006, Kyushu University. All rights reserved.