佐野坂　司 (サノサカ　ツカサ)

Sanosaka, Tsukasa

写真a

所属（所属キャンパス）

医学部 生理学教室 （信濃町）

職名

助教（有期）
このページの先頭へ▲

経歴 【 表示 ／ 非表示 】

  • 2010年04月
    -
    2013年03月

    奈良先端科学技術大学院大学, バイオサイエンス研究科, 博士研究員

  • 2013年04月
    -
    2014年03月

    九州大学, 医学部, 特任助教

このページの先頭へ▲
 

著書 【 表示 ／ 非表示 】

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

    Sanosaka Tsukasa, Tsujimura Keita, Nakashima Kinichi, 2008年03月

このページの先頭へ▲

論文 【 表示 ／ 非表示 】

  • Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation

    Isoda M., Sanosaka T., Tomooka R., Mabuchi Y., Shinozaki M., Andoh-Noda T., Banno S., Mizota N., Yamaguchi R., Okano H., Kohyama J.

    Communications Biology （Communications Biology)  6 （ 1 ）  2023年07月

    　概要を見る

    Although neural stem/progenitor cells derived from human induced pluripotent stem cells (hiPSC-NS/PCs) are expected to be a cell source for cell-based therapy, tumorigenesis of hiPSC-NS/PCs is a potential problem for clinical applications. Therefore, to understand the mechanisms of tumorigenicity in NS/PCs, we clarified the cell populations of NS/PCs. We established single cell-derived NS/PC clones (scNS/PCs) from hiPSC-NS/PCs that generated undesired grafts. Additionally, we performed bioassays on scNS/PCs, which classified cell types within parental hiPSC-NS/PCs. Interestingly, we found unique subsets of scNS/PCs, which exhibited the transcriptome signature of mesenchymal lineages. Furthermore, these scNS/PCs expressed both neural (PSA-NCAM) and mesenchymal (CD73 and CD105) markers, and had an osteogenic differentiation capacity. Notably, eliminating CD73+ CD105+ cells from among parental hiPSC-NS/PCs ensured the quality of hiPSC-NS/PCs. Taken together, the existence of unexpected cell populations among NS/PCs may explain their tumorigenicity leading to potential safety issues of hiPSC-NS/PCs for future regenerative medicine.

  • Chromatin remodeler CHD7 targets active enhancer region to regulate cell type-specific gene expression in human neural crest cells

    Sanosaka T., Okuno H., Mizota N., Andoh-Noda T., Sato M., Tomooka R., Banno S., Kohyama J., Okano H.

    Scientific Reports （Scientific Reports)  12 （ 1 ）  2022年12月

    筆頭著者

    　概要を見る

    A mutation in the chromatin remodeler chromodomain helicase DNA-binding 7 (CHD7) gene causes the multiple congenital anomaly CHARGE syndrome. The craniofacial anomalies observed in CHARGE syndrome are caused by dysfunctions of neural crest cells (NCCs), which originate from the neural tube. However, the mechanism by which CHD7 regulates the function of human NCCs (hNCCs) remains unclear. We aimed to characterize the cis-regulatory elements governed by CHD7 in hNCCs by analyzing genome-wide ChIP-Seq data and identifying hNCC-specific CHD7-binding profiles. We compared CHD7-binding regions among cell types, including human induced pluripotent stem cells and human neuroepithelial cells, to determine the comprehensive properties of CHD7-binding in hNCCs. Importantly, analysis of the hNCC-specific CHD7-bound region revealed transcription factor AP-2α as a potential co-factor facilitating the cell type-specific transcriptional program in hNCCs. CHD7 was strongly associated with active enhancer regions, permitting the expression of hNCC-specific genes to sustain the function of hNCCs. Our findings reveal the regulatory mechanisms of CHD7 in hNCCs, thus providing additional information regarding the transcriptional programs in hNCCs.

  • Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter.

    Yoshimatsu S., Seki F., Okahara J., Watanabe H., Sasaguri H., Haga Y., Hata J.i., Sanosaka T., Inoue T., Mineshige T., Lee C.Y., Shinohara H., Kurotaki Y., Komaki Y., Kishi N., Murayama A.Y., Nagai Y., Minamimoto T., Yamamoto M., Nakajima M., Zhou Z., Nemoto A., Sato T., Ikeuchi T., Sahara N., Morimoto S., Shiozawa S., Saido T.C., Sasaki E., Okano H.

    Neuroscience Research （Neuroscience Research)  185   49 - 61 2022年12月

    ISSN  01680102

    　概要を見る

    Alzheimer's disease (AD) is the leading cause of dementia which afflicts tens of millions of people worldwide. Despite many scientific progresses to dissect the AD's molecular basis from studies on various mouse models, it has been suffered from evolutionary species differences. Here, we report generation of a non-human primate (NHP), common marmoset model ubiquitously expressing Amyloid-beta precursor protein (APP) transgenes with the Swedish (KM670/671NL) and Indiana (V717F) mutations. The transgene integration of generated two transgenic marmosets (TG1&TG2) was thoroughly investigated by genomic PCR, whole-genome sequencing, and fluorescence in situ hybridization. By reprogramming, we confirmed the validity of transgene expression in induced neurons in vitro. Moreover, we discovered structural changes in specific brain regions of transgenic marmosets by magnetic resonance imaging analysis, including in the entorhinal cortex and hippocampus. In immunohistochemistry, we detected increased Aβ plaque-like structures in TG1 brain at 7 years old, although evident neuronal loss or glial inflammation was not observed. Thus, this study summarizes our attempt to establish an NHP AD model. Although the transgenesis approach alone seemed not sufficient to fully recapitulate AD in NHPs, it may be beneficial for drug development and further disease modeling by combination with other genetically engineered models and disease-inducing approaches.

  • Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms

    Ideno H., Imaizumi K., Shimada H., Sanosaka T., Nemoto A., Kohyama J., Okano H.

    iScience （iScience)  25 （ 10 ）  2022年10月

    　概要を見る

    Various culture methods have been developed for maintaining human pluripotent stem cells (PSCs). These PSC maintenance methods exhibit biased differentiation; for example, feeder-dependent PSCs efficiently yield cerebral organoids, but it is difficult to generate organoids from feeder-free PSCs. It remains unknown how PSC maintenance conditions affect differentiation. In this study, we identified fibroblast growth factor (FGF) signaling in feeder-free PSC maintenance as a key factor that determines the differentiation toward cerebral organoids. The inhibition of FGF signaling in feeder-free PSCs rescued organoid generation to the same level in feeder-dependent cultures. FGF inhibition induced DNA methylation at the WNT5A locus, and this epigenetic change suppressed the future activation of non-canonical Wnt signaling after differentiation, leading to reliable cerebral organoid generation. This study underscores the importance of PSC culture conditions for directed differentiation into cerebral organoids, and the epigenetic status regulated by FGF signaling is involved in the underlying mechanisms.

  • Coupling of angiogenesis and odontogenesis orchestrates tooth mineralization in mice

    Matsubara T., Iga T., Sugiura Y., Kusumoto D., Sanosaka T., Tai-Nagara I., Takeda N., Fong G.H., Ito K., Ema M., Okano H., Kohyama J., Suematsu M., Kubota Y.

    Journal of Experimental Medicine （Journal of Experimental Medicine)  219 （ 4 ）  2022年04月

    ISSN  00221007

    　概要を見る

    The skeletal system consists of bones and teeth, both of which are hardened via mineralization to support daily physical activity and mastication. The precise mechanism for this process, especially how blood vessels contribute to tissue mineralization, remains incompletely understood. Here, we established an imaging technique to visualize the 3D structure of the tooth vasculature at a single-cell level. Using this technique combined with single-cell RNA sequencing, we identified a unique endothelial subtype specialized to dentinogenesis, a process of tooth mineralization, termed periodontal tip-like endothelial cells. These capillaries exhibit high angiogenic activity and plasticity under the control of odontoblasts; in turn, the capillaries trigger odontoblast maturation. Metabolomic analysis demonstrated that the capillaries perform the phosphate delivery required for dentinogenesis. Taken together, our data identified the fundamental cell-to-cell communications that orchestrate tooth formation, angiogenic–odontogenic coupling, a distinct mechanism compared to the angiogenic–osteogenic coupling in bones. This mechanism contributes to our understanding concerning the functional diversity of organotypic vasculature.

全件表示 >>

このページの先頭へ▲

KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

このページの先頭へ▲

競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 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年04月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 佐野坂 司, 基盤研究(C), 補助金,  研究代表者

  • 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年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 佐野坂　司, 基盤研究(C), 補助金,  研究代表者

このページの先頭へ▲
 

担当授業科目 【 表示 ／ 非表示 】

  • 生理学Ⅱ

    2023年度

  • 生理学Ⅱ

    2022年度

  • 再生・遺伝子の科学

    2022年度, 秋学期, 講義

  • 生理学Ⅱ

    2021年度

  • 再生・遺伝子の科学

    2021年度, 秋学期, 講義

全件表示 >>

このページの先頭へ▲