Sanosaka, Tsukasa

写真a

Affiliation

School of Medicine, Department of Physiology (Shinanomachi)

Position

Instructor

Career 【 Display / hide

  • 2010.04
    -
    2013.03

    Nara Institute of Science and Technology, バイオサイエンス研究科, 博士研究員

  • 2013.04
    -
    2014.03

    Kyushu University, 医学部, 特任助教

 

Books 【 Display / hide

  • [Epigenetic regulation involved in fate specification of neural cells].

    Sanosaka Tsukasa, Tsujimura Keita, Nakashima Kinichi, 2008.03

Papers 【 Display / hide

  • Single-cell study of neural stem cells derived from human iPSCs reveals distinct progenitor populations with neurogenic and gliogenic potential

    Lam M., Sanosaka T., Lundin A., Imaizumi K., Etal D., Karlsson F.H., Clausen M., Cairns J., Hicks R., Kohyama J., Kele M., Okano H., Falk A.

    Genes to Cells (Genes to Cells)  24 ( 12 ) 836 - 847 2019.12

    ISSN  13569597

     View Summary

    © 2019 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd We used single-cell RNA sequencing (seq) on several human induced pluripotent stem (iPS) cell-derived neural stem cell (NSC) lines and one fetal brain-derived NSC line to study inherent cell type heterogeneity at proliferating neural stem cell stage and uncovered predisposed presence of neurogenic and gliogenic progenitors. We observed heterogeneity in neurogenic progenitors that differed between the iPS cell-derived NSC lines and the fetal-derived NSC line, and we also observed differences in spontaneous differentiation potential for inhibitory and excitatory neurons between the iPS cell-derived NSC lines and the fetal-derived NSC line. In addition, using a recently published glia patterning protocol we enriched for gliogenic progenitors and generated glial cells from an iPS cell-derived NSC line.

  • Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression

    Nakatsukasa H., Oda M., Yin J., Chikuma S., Ito M., Koga-Iizuka M., Someya K., Kitagawa Y., Ohkura N., Sakaguchi S., Koya I., Sanosaka T., Kohyama J., Tsukada Y.I., Yamanaka S., Takamura-Enya T., Lu Q., Yoshimura A.

    International Immunology (International Immunology)  31 ( 5 ) 335 - 347 2019

    ISSN  09538178

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    © The Japanese Society for Immunology. 2019. All rights reserved. Ten-eleven translocation (TET) proteins regulate DNA methylation and gene expression by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Although Tet2/Tet3 deficiency has been reported to lead to myeloid cell, B-cell and invariant natural killer T (iNKT) cell malignancy, the effect of TET on regulatory T cells (Tregs) has not been elucidated. We found that Tet2/Tet3 deficiency in Tregs led to lethal hyperproliferation of CD4+Foxp3+ T cells in the spleen and mesenteric lymph nodes after 5 months of age. Additionally, in aged Treg-specific Tet2/Tet3-deficient mice, serum IgG1, IgG3, IgM and IgE levels were markedly elevated. High IL-17 expression was observed in both Foxp3+ and Fopx3- CD4+ T cells, and adoptive transfer of Tet2/Tet3-deficient Tregs into lymphopenic mice inhibited Foxp3 expression and caused conversion into IL-17-producing cells. However, the conserved non-coding DNA sequence-2 (CNS2) region of the Foxp3 gene locus, which has been shown to be particularly important for stable Foxp3 expression, was only partly methylated. We identified novel TET-dependent demethylation sites in the Foxp3 upstream enhancer, which may contribute to stable Foxp3 expression. Together, these data indicate that Tet2 and Tet3 are involved in Treg stability and immune homeostasis in mice.

  • Nuclear factor I/A coordinates the timing of oligodendrocyte differentiation/maturation via olig1 promoter methylation

    Semi K., Sanosaka T., Namihira M., Nakashima K.

    HAYATI Journal of Biosciences (HAYATI Journal of Biosciences)  25 ( 2 ) 70 - 78 2018.04

    ISSN  19783019

     View Summary

    © 2018 Institut Pertanian Bogor. Transcription factors (TFs) and epigenetic modifications function cooperatively to regulate various biological processes such as cell proliferation, differentiation, maturation, and metabolism. TF binding to regulatory regions of target genes controls their transcriptional activity through alteration of the epigenetic status around the binding regions, leading to transcription network formation regulating cell fates. Although nuclear factor I/A (Nfia) is a well-known TF that induces demethylation of astrocytic genes to confer astrocytic differentiation potential on neural stem/precursor cells (NS/PCs), the epigenetic role of NFIA in oligodendrocytic lineage progression remains unclear. Here, we show that oligodendrocyte differentiation/maturation is delayed in the brains of Nfia-knockout (KO) mice, and that NFIA-regulated DNA demethylation in NS/PCs plays an important role in determining the timing of their differentiation. We further demonstrate that the promoter activity of the oligodendrocyte transcription factor 1 (Olig1) gene, involved in oligodendrocyte differentiation/maturation, is suppressed by DNA methylation, which is in turn regulated by Nfia expression. Our results suggest that NFIA controls the timing of oligodendrocytic differentiation/ maturation via demethylation of cell-type-specific gene promoters.

  • Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors

    Chai Muhchyi, Sanosaka Tsukasa, Okuno Hironobu, Zhou Zhi, Koya Ikuko, Banno Satoe, Andoh-Noda Tomoko, Tabata Yoshikuni, Shimamura Rieko, Hayashi Tetsutaro, Ebisawa Masashi, Sasagawa Yohei, Nikaido Itoshi, Okano Hideyuki, Kohyama Jun

    Genes and Development (Genes and Development)  32 ( 2 ) 165 - 180 2018.01

    ISSN  0890-9369

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    <p>Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function of chromodomain helicase DNA-binding 7 (CHD7) in NE–neural crest bifurcation, thus revealing an etiological link between the central nervous system (CNS) and craniofacial anomalies observed in CHARGE syndrome. We found that CHD7 is required for epigenetic activation of superenhancers and CNS-specific enhancers, which support the maintenance of the NE and CNS lineage identities. Furthermore, we found that BRN2 and SOX21 are downstream effectors of CHD7, which shapes cellular identities by enhancing a CNS-specific cellular program and indirectly repressing non-CNS-specific cellular programs. Based on our results, CHD7, through its interactions with superenhancer elements, acts as a regulatory hub in the orchestration of the spatiotemporal dynamics of transcription factors to regulate NE and CNS lineage identities.</p>

  • CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations

    Okuno Hironobu, Mihara Francois Renault, Ohta Shigeki, Fukuda Kimiko, Kurosawa Kenji, Akamatsu Wado, Sanosaka Tsukasa, Kohyama Jun, Hayashi Kanehiro, Nakajima Kazunori, Takahashi Takao, Wysocka Joanna, Kosaki Kenjiro, Okano Hideyuki

    eLife 6 2017.11

    ISSN  2050-084X

     View Summary

    <p>CHARGE syndrome is caused by heterozygous mutations in the chromatin remodeler, CHD7, and is characterized by a set of malformations that, on clinical grounds, were historically postulated to arise from defects in neural crest formation during embryogenesis. To better delineate neural crest defects in CHARGE syndrome, we generated induced pluripotent stem cells (iPSCs) from two patients with typical syndrome manifestations, and characterized neural crest cells differentiated in vitro from these iPSCs (iPSC-NCCs). We found that expression of genes associated with cell migration was altered in CHARGE iPSC-NCCs compared to control iPSC-NCCs. Consistently, CHARGE iPSC-NCCs showed defective delamination, migration and motility in vitro, and their transplantation in ovo revealed overall defective migratory activity in the chick embryo. These results support the historical inference that CHARGE syndrome patients exhibit defects in neural crest migration, and provide the first successful application of patient-derived iPSCs in modeling craniofacial disorders.</p>

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 神経幹細胞の分化能を規定するDNAメチル化変動の解明

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 佐野坂 司, Grant-in-Aid for Scientific Research (C), Principal Investigator

 

Courses Taught 【 Display / hide

  • PHYSIOLOGY 2

    2020

  • PHYSIOLOGY 2

    2019