2022/01/27 更新

写真a

ビゼン ノリヒサ
備前 典久
BIZEN Norihisa
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 生体機能調節医学専攻 機能再建医学 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2013年3月   東京医科歯科大学 )

研究キーワード

  • 神経解剖学

  • アストロサイト

  • グリア

  • 神経発生

  • 神経幹細胞

  • オリゴデンドロサイト

  • Olig2

研究分野

  • ライフサイエンス / 神経形態学

  • ライフサイエンス / 神経科学一般

  • ライフサイエンス / 解剖学

  • ライフサイエンス / 発生生物学

経歴(researchmap)

  • 新潟大学   大学院医歯学総合研究科 神経生物・解剖学分野   助教

    2015年6月 - 現在

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  • 新潟大学   大学院医歯学総合研究科 神経生物・解剖学分野   博士研究員

    2014年4月 - 2015年5月

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  • 東京医科歯科大学   難治疾患研究所 幹細胞制御分野   特任助教

    2014年1月 - 2014年3月

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  • 東京医科歯科大学   難治疾患研究所 幹細胞制御分野   技術補佐員

    2013年4月 - 2013年12月

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経歴

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 機能再建医学   助教

    2015年6月 - 現在

学歴

  • 東京医科歯科大学   大学院医歯学総合研究科

    - 2013年3月

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  • 熊本大学   薬学部   薬科学科

    - 2007年3月

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所属学協会

 

論文

  • Ddx20, an Olig2 binding factor, governs the survival of neural and oligodendrocyte progenitor cells via proper Mdm2 splicing and p53 suppression 査読

    Norihisa Bizen, Asim K. Bepari, Li Zhou, Manabu Abe, Kenji Sakimura, Katsuhiko Ono, Hirohide Takebayashi

    Cell Death & Differentiation   2022年1月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>Olig2 is indispensable for motoneuron and oligodendrocyte fate-specification in the pMN domain of embryonic spinal cords, and also involved in the proliferation and differentiation of several cell types in the nervous system, including neural progenitor cells (NPCs) and oligodendrocytes. However, how Olig2 controls these diverse biological processes remains unclear. Here, we demonstrated that a novel Olig2-binding protein, DEAD-box helicase 20 (Ddx20), is indispensable for the survival of NPCs and oligodendrocyte progenitor cells (OPCs). A central nervous system (CNS)-specific <italic>Ddx20</italic> conditional knockout (cKO) demonstrated apoptosis and cell cycle arrest in NPCs and OPCs, through the potentiation of the p53 pathway in DNA damage-dependent and independent manners, including SMN complex disruption and the abnormal splicing of <italic>Mdm2</italic> mRNA. Analyzes of <italic>Olig2</italic> null NPCs showed that Olig2 contributed to NPC proliferation through Ddx20 protein stabilization. Our findings provide novel mechanisms underlying the Olig2-mediated proliferation of NPCs, via the Ddx20-p53 axis, in the embryonic CNS.

    DOI: 10.1038/s41418-021-00915-8

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    その他リンク: https://www.nature.com/articles/s41418-021-00915-8

  • Ddx20, DEAD box helicase 20, is essential for the differentiation of oligodendrocyte and maintenance of myelin gene expression. 査読 国際誌

    *Anna Simankova, *Norihisa Bizen, Sei Saitoh, Shinsuke Shibata, Nobuhiko Ohno, Manabu Abe, Kenji Sakimura, Hirohide Takebayashi, (*contributed equally)

    Glia   2021年7月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Oligodendrocytes form myelin sheaths that surround axons, contributing to saltatory conduction and proper central nervous system (CNS) function. Oligodendrocyte progenitor cells (OPCs) are generated during the embryonic stage and differentiate into myelinating oligodendrocytes postnatally. Ddx20 is a multifunctional, DEAD-box helicase involved in multiple cellular processes, including transcription, splicing, microRNA biogenesis, and translation. Although defects in each of these processes result in abnormal oligodendrocyte differentiation and myelination, the involvement of Ddx20 in oligodendrocyte terminal differentiation remains unknown. To address this question, we used Mbp-Cre mice to generate Ddx20 conditional knockout (cKO) mice to allow for the deletion of Ddx20 from mature oligodendrocytes. Mbp-Cre;Ddx20 cKO mice demonstrated small body sizes, behavioral abnormalities, muscle weakness, and short lifespans, with mortality by the age of 2 months old. Histological analyses demonstrated significant reductions in the number of mature oligodendrocytes and drastic reductions in the expression levels of myelin-associated mRNAs, such as Mbp and Plp at postnatal day 42. The number of OPCs did not change. A thin myelin layer was observed for large-diameter axons in Ddx20 cKO mice, based on electron microscopic analysis. A bromodeoxyuridine (BrdU) labeling experiment demonstrated that terminal differentiation was perturbed from ages 2 weeks to 7 weeks in the CNS of Mbp-Cre;Ddx20 cKO mice. The activation of mitogen-activated protein (MAP) kinase, which promotes myelination, was downregulated in the Ddx20 cKO mice based on immunohistochemical detection. These results indicate that Ddx20 is an essential factor for terminal differentiation of oligodendrocytes and maintenance of myelin gene expression.

    DOI: 10.1002/glia.24058

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  • Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons. 査読 国際誌

    Ya-Zhou Wang, Hong Fan, Yu Ji, Kurt Reynolds, Ran Gu, Qini Gan, Takashi Yamagami, Tianyu Zhao, Salaheddin Hamad, Norihisa Bizen, Hirohide Takebayashi, YiPing Chen, Shengxi Wu, David Pleasure, Kit Lam, Chengji J Zhou

    Cellular and molecular life sciences : CMLS   77 ( 18 )   3597 - 3609   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons.

    DOI: 10.1007/s00018-019-03385-x

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  • Glial pathology in a novel spontaneous mutant mouse of the Eif2b5 gene: a vanishing white matter disease model. 査読 国際誌

    Mika Terumitsu-Tsujita, Hiroki Kitaura, Ikuo Miura, Yuji Kiyama, Fumiko Goto, Yoshiko Muraki, Shiho Ominato, Norikazu Hara, Anna Simankova, Norihisa Bizen, Kazuhiro Kashiwagi, Takuhiro Ito, Yasuko Toyoshima, Akiyoshi Kakita, Toshiya Manabe, Shigeharu Wakana, Hirohide Takebayashi, Hironaka Igarashi

    Journal of neurochemistry   154 ( 1 )   25 - 40   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vanishing white matter disease (VWM) is an autosomal recessive neurological disorder caused by mutation(s) in any subunit of eukaryotic translation initiation factor 2B (eIF2B), an activator of translation initiation factor eIF2. VWM occurs with mutation of the genes encoding eIF2B subunits (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5). However, little is known regarding the underlying pathogenetic mechanisms or how to treat patients with VWM. Here we describe the identification and detailed analysis of a new spontaneous mutant mouse harboring a point mutation in the Eif2b5 gene (p.Ile98Met). Homozygous Eif2b5I98M mutant mice exhibited a small body, abnormal gait, male and female infertility, epileptic seizures, and a shortened lifespan. Biochemical analyses indicated that the mutant eIF2B protein with the Eif2b5I98M mutation decreased guanine nucleotide exchange activity on eIF2, and the level of the endoplasmic reticulum stress marker activating transcription factor 4 was elevated in the 1-month-old Eif2b5I98M brain. Histological analyses indicated up-regulated glial fibrillary acidic protein immunoreactivity in the astrocytes of the Eif2b5I98M forebrain and translocation of Bergmann glia in the Eif2b5I98M cerebellum, as well as increased mRNA expression of an endoplasmic reticulum stress marker, C/EBP homologous protein. Disruption of myelin and clustering of oligodendrocyte progenitor cells were also indicated in the white matter of the Eif2b5I98M spinal cord at 8 months old. Our data show that Eif2b5I98M mutants are a good model for understanding VWM pathogenesis and therapy development. Cover Image for this issue: doi: 10.1111/jnc.14751.

    DOI: 10.1111/jnc.14887

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  • Diverse dystonin gene mutations cause distinct patterns of Dst isoform deficiency and phenotypic heterogeneity in Dystonia musculorum mice. 査読 国際誌

    Nozomu Yoshioka, Yudai Kabata, Momona Kuriyama, Norihisa Bizen, Li Zhou, Dang M Tran, Masato Yano, Atsushi Yoshiki, Tatsuo Ushiki, Thomas J Sproule, Riichiro Abe, Hirohide Takebayashi

    Disease models & mechanisms   13 ( 5 )   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Loss-of-function mutations in dystonin (DST) can cause hereditary sensory and autonomic neuropathy type 6 (HSAN-VI) or epidermolysis bullosa simplex (EBS). Recently, DST-related diseases were recognized to be more complex than previously thought because a patient exhibited both neurological and skin manifestations, whereas others display only one or the other. A single DST locus produces at least three major DST isoforms: DST-a (neuronal isoform), DST-b (muscular isoform) and DST-e (epithelial isoform). Dystonia musculorum (dt) mice, which have mutations in Dst, were originally identified as spontaneous mutants displaying neurological phenotypes. To reveal the mechanisms underlying the phenotypic heterogeneity of DST-related diseases, we investigated two mutant strains with different mutations: a spontaneous Dst mutant (Dstdt-23Rbrc mice) and a gene-trap mutant (DstGt mice). The Dstdt-23Rbrc allele possesses a nonsense mutation in an exon shared by all Dst isoforms. The DstGt allele is predicted to inactivate Dst-a and Dst-b isoforms but not Dst-e There was a decrease in the levels of Dst-a mRNA in the neural tissue of both Dstdt-23Rbrc and DstGt homozygotes. Loss of sensory and autonomic nerve ends in the skin was observed in both Dstdt-23Rbrc and DstGt mice at postnatal stages. In contrast, Dst-e mRNA expression was reduced in the skin of Dstdt-23Rbrc mice but not in DstGt mice. Expression levels of Dst proteins in neural and cutaneous tissues correlated with Dst mRNAs. Because Dst-e encodes a structural protein in hemidesmosomes (HDs), we performed transmission electron microscopy. Lack of inner plaques and loss of keratin filament invasions underneath the HDs were observed in the basal keratinocytes of Dstdt-23Rbrc mice but not in those of DstGt mice; thus, the distinct phenotype of the skin of Dstdt-23Rbrc mice could be because of failure of Dst-e expression. These results indicate that distinct mutations within the Dst locus can cause different loss-of-function patterns among Dst isoforms, which accounts for the heterogeneous neural and skin phenotypes in dt mice and DST-related diseases.

    DOI: 10.1242/dmm.041608

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  • Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy. 査読 国際誌

    Mikko Muona, Ryosuke Ishimura, Anni Laari, Yoshinobu Ichimura, Tarja Linnankivi, Riikka Keski-Filppula, Riitta Herva, Heikki Rantala, Anders Paetau, Minna Pöyhönen, Miki Obata, Takefumi Uemura, Thomas Karhu, Norihisa Bizen, Hirohide Takebayashi, Shane McKee, Michael J Parker, Nadia Akawi, Jeremy McRae, Matthew E Hurles, Outi Kuismin, Mitja I Kurki, Anna-Kaisa Anttonen, Keiji Tanaka, Aarno Palotie, Satoshi Waguri, Anna-Elina Lehesjoki, Masaaki Komatsu

    American journal of human genetics   99 ( 3 )   683 - 694   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBA5, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBA5 variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.Ala371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg55His, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.Ala371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufm1 in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.Ala371Thr variant in trans with a loss-of-function allele in UBA5 underlies a severe infantile-onset encephalopathy.

    DOI: 10.1016/j.ajhg.2016.06.020

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  • A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche. 査読 国際誌

    Kouichi Tabu, Nozomi Muramatsu, Christian Mangani, Mei Wu, Rong Zhang, Taichi Kimura, Kazuo Terashima, Norihisa Bizen, Ryosuke Kimura, Wenqian Wang, Yoshitaka Murota, Yasuhiro Kokubu, Ikuo Nobuhisa, Tetsushi Kagawa, Issay Kitabayashi, Mark Bradley, Tetsuya Taga

    Stem cells (Dayton, Ohio)   34 ( 5 )   1151 - 62   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs. Iron is stored in tumor infiltrating host macrophages (Mφs), whose protumoral activity is potently enhanced by SP cell-secreted soluble factor(s). Finally, coexpression of ECM-, iron-, and Mφ-related genes is found to be predictive of glioma patients' outcome. Our polymer-based approach reveals the intrinsic capacities of GSCs, to adapt the environment to organize a self-advantageous microenvironment niche, for their maintenance and expansion, which redefines the current concept of anti-CSC niche therapy and has the potential to accelerate cancer therapy development. Stem Cells 2016;34:1151-1162.

    DOI: 10.1002/stem.2299

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  • Endoplasmic Reticulum-Localized Transmembrane Protein Dpy19L1 Is Required for Neurite Outgrowth. 査読 国際誌

    Keisuke Watanabe, Norihisa Bizen, Noboru Sato, Hirohide Takebayashi

    PloS one   11 ( 12 )   e0167985   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    The endoplasmic reticulum (ER), including the nuclear envelope, is a continuous and intricate membrane-bound organelle responsible for various cellular functions. In neurons, the ER network is found in cell bodies, axons, and dendrites. Recent studies indicate the involvement of the ER network in neuronal development, such as neuronal migration and axonal outgrowth. However, the regulation of neural development by ER-localized proteins is not fully understood. We previously reported that the multi-transmembrane protein Dpy19L1 is required for neuronal migration in the developing mouse cerebral cortex. A Dpy19L family member, Dpy19L2, which is a causative gene for human Globozoospermia, is suggested to act as an anchor of the acrosome to the nuclear envelope. In this study, we found that the patterns of exogenous Dpy19L1 were partially coincident with the ER, including the nuclear envelope in COS-7 cells at the level of the light microscope. The reticular distribution of Dpy19L1 was disrupted by microtubule depolymerization that induces retraction of the ER. Furthermore, Dpy19L1 showed a similar distribution pattern with a ER marker protein in embryonic mouse cortical neurons. Finally, we showed that Dpy19L1 knockdown mediated by siRNA resulted in decreased neurite outgrowth in cultured neurons. These results indicate that transmembrane protein Dpy19L1 is localized to the ER membrane and regulates neurite extension during development.

    DOI: 10.1371/journal.pone.0167985

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  • A growth-promoting signaling component cyclin D1 in neural stem cells has antiastrogliogenic function to execute self-renewal. 査読 国際誌

    Bizen N, Inoue T, Shimizu T, Tabu K, Kagawa T, Taga T

    Stem Cells   32 ( 6 )   1602 - 15   2014年6月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Self-renewing proliferation of neural stem cells (NSCs) is intimately linked to the inhibition of neuronal and glial differentiation, however, their molecular linkage has been poorly understood. We have proposed a model previously explaining partly this linkage, in which fibroblast growth factor 2 (FGF2) and Wnt signals cooperate to promote NSC self-renewal via beta-catenin accumulation, which leads to the promotion of proliferation by lymphoid enhancer factor (LEF)/T-cell factor (TCF)-mediated cyclin D1 expression and at the same time to the inhibition of neuronal differentiation by beta-catenin-mediated potentiation of Notch signaling. To fully understand the mechanisms underlying NSC self-renewal, it needs to be clarified how these growth factor signals inhibit glial differentiation as well. Here, we demonstrate that cyclin D1, a NSC growth promoting signaling component and also a common component of FGF2 and Wnt signaling pathways, inhibits astroglial differentiation of NSCs. Interestingly, this effect of cyclin D1 is mediated even though its cell cycle progression activity is blocked. Forced downregulation of cyclin D1 enhances astrogliogenesis of NSCs in culture and in viv

    DOI: 10.1002/stem.1613

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  • [Roles of GSK3beta signaling in the self-renewal of neural progenitor cells].

    Tetsushi Kagawa, Norihisa Bizen, Norihisa Bizen, Tetsuya Taga

    Seikagaku. The Journal of Japanese Biochemical Society   86 ( 1 )   68 - 71   2014年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Gene Regulation of Prominin-1 (CD133) in Normal and Cancerous Tissues. 査読 国際誌

    Kouichi Tabu, Norihisa Bizen, Tetsuya Taga, Shinya Tanaka

    Advances in experimental medicine and biology   777   73 - 85   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    A pentaspan membrane glycoprotein prominin-1 (frequently called CD133 in human) is widely used as a surface marker to identify and isolate normal stem/progenitor cells from various organs, although it is also expressed in some types of differentiated cells. Since CD133 was identified as a universal marker to isolate cancer stem cells (CSCs) in tumors derived from multiple tissues, much attention has been directed toward the relationship between its gene regulation and identity of CSCs (i.e., cancer stemness). Prominin-1 (PROM1) gene possesses five alternative promoters yielding multiple first exons within the 5'-untranslated region (UTR) and also splicing variants affecting the open reading frame (ORF) sequence, implicating the complicated gene regulation in a context-dependent manner. This chapter aims to organize the accumulated findings on prominin-1 with a focus on its altered expression and regulation in normal and cancerous cells and to discuss potential regulatory networks underlying cancer stemness.

    DOI: 10.1007/978-1-4614-5894-4_5

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  • Analysis of an alternative human CD133 promoter reveals the implication of Ras/ERK pathway in tumor stem-like hallmarks. 査読 国際誌

    Kouichi Tabu, Taichi Kimura, Ken Sasai, Lei Wang, Norihisa Bizen, Hiroshi Nishihara, Tetsuya Taga, Shinya Tanaka

    Molecular cancer   9 ( 39 )   39 - 39   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    BACKGROUND: An increasing number of studies support the presence of stem-like cells in human malignancies. These cells are primarily responsible for tumor initiation and thus considered as a potential target to eradicate tumors. CD133 has been identified as an important cell surface marker to enrich the stem-like population in various human tumors. To reveal the molecular machinery underlying the stem-like features in tumor cells, we analyzed a promoter of CD133 gene using human colon carcinoma Caco-2 and synovial sarcoma Fuji cells, which endogenously express CD133 gene. RESULTS: A reporter analysis revealed that P5 promoter, located far upstream in a human CD133 gene locus, exhibits the highest activity among the five putative promoters (P1 to P5). Deletion and mutation analysis identified two ETS binding sites in the P5 region as being essential for its promoter activity. Electrophoretic mobility shift assays demonstrated the specific binding between nuclear factors and the ETS binding sequence. Overexpression of dominant-negative forms of Ets2 and Elk1 resulted in the significant decrease of P5 activity. Furthermore, treatment of Fuji cells with a specific MEK/ERK inhibitor, U0126, also markedly decreased CD133 expression, but there was no significant effect in Caco-2 cells, suggesting cell type-specific regulation of CD133 expression. Instead, the side population, another hallmark of TSLCs, was dramatically diminished in Caco-2 cells by U0126. Finally, Ras-mediated oncogenic transformation in normal human astrocytes conferred the stem-like capability to form neurosphere-like colonies with the increase of CD133 mRNA expression. CONCLUSIONS: In conclusion, the Ras/ERK pathway at least in part contributes to the maintenance and the acquisition of stem-like hallmarks, although the extent of its contribution is varied in a cell type-specific manner. These findings could help our comprehensive understanding of tumor stemness, and also improve the development of eradicative therapies against human malignancies.

    DOI: 10.1186/1476-4598-9-39

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▶ 全件表示

書籍等出版物

  • 神経幹細胞の分化制御機構:細胞外来生シグナルと細胞内在性プログラムによる分化制御

    備前典久, 鹿川哲史, 田賀哲也( 担当: 分担執筆 ,  範囲: 再生医療シリーズ 脳神経系の発生・再生の融合的新展開 28-33ページ)

    診断と治療社  2015年1月 

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  • GSK3bシグナル経路による神経前駆細胞の自己複製制御

    鹿川哲史, 備前典久, 清水健史, 田賀哲也( 担当: 分担執筆 ,  範囲: 生化学 第86巻第1号 68-71ページ)

    日本生化学会  2014年 

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  • LIF (Leukemia Inhibitory Factor)

    備前典久, 田賀哲也( 担当: 分担執筆 ,  範囲: 臨床免疫・アレルギー科 増刊 「サイトカインのすべて」Vol.57 545-552ページ)

    科学評論社  2012年 

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  • アストロサイトの発生・分化

    鹿川哲史, 備前典久, 田賀哲也( 担当: 分担執筆 ,  範囲: Clinical Neuroscience 別冊, Vol 29, No.11, Page 1239-1242)

    中外医学社  2011年 

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  • 第2章 細胞 (その他の幹細胞など)-ものづくりから考察する幹細胞の居心地-

    田賀哲也, 椨康一, 備前典久( 担当: 分担執筆 ,  範囲: ものづくり技術からみる再生医療-細胞研究・創薬・治療- Page 18-24)

    シーエムシー出版  2011年 

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MISC

  • RNA代謝調節因子Ddx20による神経前駆細胞およびオリゴデンドロサイト前駆細胞維持機構

    備前典久, 竹林浩秀

    神経化学トピックス   2022年1月

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受賞

  • 大会長賞

    2021年9月   第109回日本解剖学会関東支部学術集会  

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  • 若手優秀発表賞

    2017年12月   次世代脳プロジェクト・冬のシンポジウム   Identification of a novel Olig2-binding factor indispensable for oligodendrogenesis in central nervous system

    備前 典久

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  • 優秀論文賞

    2014年3月   東京医科歯科大学 難治疾患研究所   A growth-promoting signaling component cyclin D1 in neural stem cells has anti-astrogliogenic function to execute self-renewal. Stem Cells, 32:1602-1615, 2014

    備前 典久

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共同研究・競争的資金等の研究

  • オリゴデンドロサイト機能異常が惹起するp53誘導性神経変性機構の分子基盤解明

    研究課題/領域番号:20K07241  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    備前 典久

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • ミエリン形成における転写-RNA代謝カップリング機構の分子基盤解明

    研究課題/領域番号:17K15542  2017年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    備前 典久

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    本研究はオリゴデンドロサイト(OL)分化に必須の分子として同定したOlig2-binding protein2 (Obp2)のミエリン形成過程の機能を解明することを目的としている。昨年度は、MBP-Creを用いたOL最終分化過程におけるObp2欠損マウス(MBP-Cre; Obp2 cKOマウス)の解析を行い、脳内および脊髄内の成熟OLマーカーが生後6週齢で顕著に減少し、ミエリンの低形成が認められたことを報告した。今年度は、まず別のOL系譜特異的Obp2欠損マウス(Cnp-Cre; Obp2 cKOマウス)を作製し、OL分化への影響を検証した。しかし、このマウス胎生期脊髄においてOL前駆細胞の数が著しく減少し、OL分化が本格化する前の出生直後に死亡した。次に、MBP-Cre; Obp2 cKOマウスにおけるミエリン低形成の出現時期を免疫組織化学およびin situ hybridization法で検討したところ、Obp2欠損脊髄では、成熟OLマーカーであるCC-1、PLP、MBPの発現は生後2週齢まで顕著な変化は見られず、生後3週齢で有意に減少した。また、このマウスで認められた末梢神経異常の原因を解析したところ、坐骨神経周囲において1部のシュワン細胞関連遺伝子の発現が顕著に低下していた。次に、Obp2欠損脊髄におけるRNA-seqによるトランスクリプトーム解析を行ったところ、OL分化およびミエリン化に関与する遺伝子群の発現低下とpre-mRNAスプライシング異常が検出された。これらは発現低下とスプライシング異常が共に検出された遺伝子群と、発現低下あるいはスプライシング異常のみ検出された群に分けられた。この結果からObp2がOL分化およびミエリン関連遺伝子の発現とpre-mRNAスプライシング制御のそれぞれ、あるいは両方を担っている可能性が示唆された。

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  • 小脳失調症状を呈するRNA代謝-ミエリン形成異常マウスの解析

    2017年 - 2018年

    塚田医学奨学基金  平成29年度 塚田医学奨学助成金 

    備前 典久

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    担当区分:研究代表者  資金種別:競争的資金

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  • 新規Olig2結合候補因子によるオリゴデンドロサイト分化促進機構の解明とその応用

    研究課題/領域番号:15K18373  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    備前 典久

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    オリゴデンドロサイト(OL)発生に必須の転写因子であるOlig2の新規結合分子として同定したObp2の中枢神経系特異的ノックアウトマウスの解析から、Obp2がDNA損傷-p53経路の制御を介して、神経前駆細胞およびOL前駆細胞の維持に必須であること、Obp2のtruncated formであるOIFがOL関連遺伝子の転写を促進することでOL分化を強力に誘導することを明らかにした。

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  • 人工幹細胞ニッチを用いた神経幹細胞の未分化性維持 と分化を制御する分子基盤解明

    2012年 - 2013年

    東京医科歯科大学 難治疾患研究所  難治疾患研究所研究助成 

    備前 典久

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    担当区分:研究代表者  資金種別:競争的資金

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担当経験のある授業科目(researchmap)

  • 神経解剖学

    機関名:新潟大学

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  • 医学研究実習

    機関名:新潟大学

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  • 卒業研究実習

    機関名:新潟大学 医学部保健学科

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  • 発生学

    機関名:新潟大学

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  • 神経解剖実習

    機関名:新潟大学

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