Sanosaka, Tsukasa

写真a

Affiliation

School of Medicine, Department of Physiology （Shinanomachi）

Position

Instructor
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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

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Books 【 Display / hide 】

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

    Sanosaka Tsukasa, Tsujimura Keita, Nakashima Kinichi, 2008.03

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Papers 【 Display / hide 】

  • Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species

    Yoshimatsu S., Nakajima M., Iguchi A., Sanosaka T., Sato T., Nakamura M., Nakajima R., Arai E., Ishikawa M., Imaizumi K., Watanabe H., Okahara J., Noce T., Takeda Y., Sasaki E., Behr R., Edamura K., Shiozawa S., Okano H.

    Stem Cell Reports （Stem Cell Reports)  16 （ 4 ） 754 - 770 2021.04

    ISSN  22136711

    　View Summary

    Induced pluripotent stem cells (iPSCs) are capable of providing an unlimited source of cells from all three germ layers and germ cells. The derivation and usage of iPSCs from various animal models may facilitate stem cell-based therapy, gene-modified animal production, and evolutionary studies assessing interspecies differences. However, there is a lack of species-wide methods for deriving iPSCs, in particular by means of non-viral and non-transgene-integrating (NTI) approaches. Here, we demonstrate the iPSC derivation from somatic fibroblasts of multiple mammalian species from three different taxonomic orders, including the common marmoset (Callithrix jacchus) in Primates, the dog (Canis lupus familiaris) in Carnivora, and the pig (Sus scrofa) in Cetartiodactyla, by combinatorial usage of chemical compounds and NTI episomal vectors. Interestingly, the fibroblasts temporarily acquired a neural stem cell-like state during the reprogramming. Collectively, our method, robustly applicable to various species, holds a great potential for facilitating stem cell-based research using various animals in Mammalia.

  • A robust culture system to generate neural progenitors with gliogenic competence from clinically relevant induced pluripotent stem cells for treatment of spinal cord injury

    Kamata Y., Isoda M., Sanosaka T., Shibata R., Ito S., Okubo T., Shinozaki M., Inoue M., Koya I., Shibata S., Shindo T., Matsumoto M., Nakamura M., Okano H., Nagoshi N., Kohyama J.

    Stem Cells Translational Medicine （Stem Cells Translational Medicine)  10 （ 3 ） 398 - 413 2021.03

    ISSN  21576564

    　View Summary

    Cell-based therapy targeting spinal cord injury (SCI) is an attractive approach to promote functional recovery by replacing damaged tissue. We and other groups have reported the effectiveness of transplanting neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) in SCI animal models for neuronal replacement. Glial replacement is an additional approach for tissue repair; however, the lack of robust procedures to drive iPSCs into NS/PCs which can produce glial cells has hindered the development of glial cell transplantation for the restoration of neuronal functions after SCI. Here, we established a method to generate NS/PCs with gliogenic competence (gNS/PCs) optimized for clinical relevance and utilized them as a source of therapeutic NS/PCs for SCI. We could successfully generate gNS/PCs from clinically relevant hiPSCs, which efficiently produced astrocytes and oligodendrocytes in vitro. We also performed comparison between gNS/PCs and neurogenic NS/PCs based on single cell RNA-seq analysis and found that gNS/PCs were distinguished by expression of several transcription factors including HEY2 and NFIB. After gNS/PC transplantation, the graft did not exhibit tumor-like tissue formation, indicating the safety of them as a source of cell therapy. Importantly, the gNS/PCs triggered functional recovery in an SCI animal model, with remyelination of demyelinated axons and improved motor function. Given the inherent safety of gNS/PCs and favorable outcomes observed after their transplantation, cell-based medicine using the gNS/PCs-induction procedure described here together with clinically relevant iPSCs is realistic and would be beneficial for SCI patients.

  • 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

    　View Summary

    © 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.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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

  • 神経幹細胞特異的なエンハンサーによる遺伝子発現制御機構の解明

    2021.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 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, Grant-in-Aid for Scientific Research (C), Principal investigator

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Courses Taught 【 Display / hide 】

  • PHYSIOLOGY 2

    2022

  • PHYSIOLOGY 2

    2021

  • PHYSIOLOGY 2

    2020

  • PHYSIOLOGY 2

    2019

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