洪　実 （コウ　ミノル）

Ko, Minoru

写真a

所属（所属キャンパス）

医学部 （三田）

職名

名誉教授

HP

外部リンク
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経歴 【 表示 ／ 非表示 】

  • 1988年04月
    -
    1991年07月

    科学技術庁（旧）、新技術事業団、創造科学推進事業, 古澤発生遺伝子プロジェクト、遺伝子発現グループ, 研究員

  • 1991年08月
    -
    1992年08月

    科学技術庁（旧）、新技術事業団、創造科学推進事業, 古澤発生遺伝子プロジェクト、遺伝子発現グループ, グループリーダー

  • 1992年09月
    -
    1997年08月

    米国ミシガン州立ウェインステイト大学、医学部, 分子医学遺伝学センター, 助教授

  • 1997年09月
    -
    1998年08月

    米国ミシガン州立ウェインステイト大学、医学部、, 分子医学遺伝学センター、内科学教室, 准教授（終身在職権）

  • 1998年09月
    -
    2011年12月

    米国国立衛生研究所、国立老化研究所, 発生老化ゲノム学部門, 主任研究員（終身在職権）、部門長

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学歴 【 表示 ／ 非表示 】

  • 1980年04月
    -
    1986年03月

    慶應義塾大学, 医学部

    大学, 卒業

  • 1986年04月
    -
    1988年03月

    慶應義塾大学, 医学研究科

    大学院, 退学, 博士

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学位 【 表示 ／ 非表示 】

  • 医学博士, 慶應義塾大学, 論文, 1991年07月

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免許・資格 【 表示 ／ 非表示 】

  • 医師免許, 1986年

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著書 【 表示 ／ 非表示 】

  • Harrison's Principles of Internal Medicine, 19th Edition

    洪 実, McGraw-Hill, 2015年

    担当範囲: Stem Cell Biology

  • Harrison's Principles of Internal Medicine, 18th Edition

    洪 実, McGraw-Hill, 2011年

    担当範囲: Stem Cell Biology

  • Harrison's Principles of Internal Medicine, 17th Edition

    洪 実, McGraw-Hill, 2008年

    担当範囲: Stem Cell Biology

  • Human Pluripotent Stem Cells

    洪 実, BIOS Scientific Publishers, 2004年

    担当範囲: Genomic approaches to stem cell biology

  • Mammalian Genomics

    洪 実, CABI Publishing, 2004年

    担当範囲: Regulation of genome activity and genetic networks in mammals

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論文 【 表示 ／ 非表示 】

  • SCODE

    Matsumoto Hirotaka, Kiryu Hisanori, Furusawa Chikara, Ko Minoru S.H., Ko Shigeru B.H., Gouda Norio, Hayashi Tetsutaro, Nikaido Itoshi

    Bioinformatics 33 （ 15 ） 2314 - 2321 2017年08月

    ISSN  1367-4803

    　概要を見る

    <p>Motivation: The analysis of RNA-Seq data from individual differentiating cells enables us to reconstruct the differentiation process and the degree of differentiation (in pseudo-time) of each cell. Such analyses can reveal detailed expression dynamics and functional relationships for differentiation. To further elucidate differentiation processes, more insight into gene regulatory networks is required. The pseudo-time can be regarded as time information and, therefore, single-cell RNASeq data are time-course data with high time resolution. Although time-course data are useful for inferring networks, conventional inference algorithms for such data suffer from high time complexity when the number of samples and genes is large. Therefore, a novel algorithm is necessary to infer networks from single-cell RNA-Seq during differentiation. Results: In this study, we developed the novel and efficient algorithm SCODE to infer regulatory networks, based on ordinary differential equations. We applied SCODE to three single-cell RNASeq datasets and confirmed that SCODE can reconstruct observed expression dynamics. We evaluated SCODE by comparing its inferred networks with use of a DNaseI-footprint based network. The performance of SCODE was best for two of the datasets and nearly best for the remaining dataset. We also compared the runtimes and showed that the runtimes for SCODE are significantly shorter than for alternatives. Thus, our algorithm provides a promising approach for further singlecell differentiation analyses.</p>

  • Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors

    Matsushita Misako, Nakatake Yuhki, Arai Itaru, Ibata Keiji, Kohda Kazuhisa, Goparaju Sravan K., Murakami Miyako, Sakota Miki, Chikazawa-Nohtomi Nana, Ko Shigeru B.H., Kanai Takanori, Yuzaki Michisuke, Ko Minoru S.H.

    Biochemical and Biophysical Research Communications 2017年05月

    ISSN  0006-291X

    　概要を見る

    <p>Pluripotent human embryonic stem cells (hESCs) can differentiate into multiple cell lineages, thus, providing one of the best platforms to study molecular mechanisms during cell differentiation. Recently, we have reported rapid and efficient differentiation of hESCs into functional neurons by introducing a cocktail of synthetic mRNAs encoding five transcription factors (TFs): NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. Here we further tested a possibility that even single transcription factors, when expressed ectopically, can differentiate hESCs into neurons. To this end, we established hESC lines in which each of these TFs can be overexpressed by the doxycycline-inducible piggyBac vector. The overexpression of any of these five TFs indeed caused a rapid and rather uniform differentiation of hESCs, which were identified as neurons based on their morphologies, qRT-PCR, and immunohistochemistry. Furthermore, calcium-imaging analyses and patch clamp recordings demonstrated that these differentiated cells are electrophysiologically functional. Interestingly, neural differentiations occurred despite the cell culture conditions that rather promote the maintenance of the undifferentiated state. These results indicate that over-expression of each of these five TFs can override the pluripotency-specific gene network and force hESCs to differentiate into neurons.</p>

  • Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors

    Goparaju Sravan Kumar, Kohda Kazuhisa, Ibata Keiji, Soma Atsumi, Nakatake Yukhi, Akiyama Tomohiko, Wakabayashi Shunichi, Matsushita Misako, Sakota Miki, Kimura Hiromi, Yuzaki Michisuke, Ko Shigeru B H, Ko Minoru S H

    Scientific Reports 7 2017年02月

    ISSN  2045-2322

    　概要を見る

    <p>Efficient differentiation of human pluripotent stem cells (hPSCs) into neurons is paramount for disease modeling, drug screening, and cell transplantation therapy in regenerative medicine. In this manuscript, we report the capability of five transcription factors (TFs) toward this aim: NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. In contrast to previous methods that have shortcomings in their speed and efficiency, a cocktail of these TFs as synthetic mRNAs can differentiate hPSCs into neurons in 7 days, judged by calcium imaging and electrophysiology. They exhibit motor neuron phenotypes based on immunostaining. These results indicate the establishment of a novel method for rapid, efficient, and footprint-free differentiation of functional neurons from hPSCs.</p>

  • Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells

    Akiyama Tomohiko, Wakabayashi Shunichi, Soma Atsumi, Sato Saeko, Nakatake Yuhki, Oda Mayumi, Murakami Miyako, Sakota Miki, Chikazawa-Nohtomi Nana, Ko Shigeru B.H., Ko Minoru S.H.

    Stem Cells International 2017 2017年

    　概要を見る

    <p>Human pluripotent stem cells (hPSCs) have the capacity to differentiate into essentially all cell types in the body. Such differentiation can be directed to specific cell types by appropriate cell culture conditions or overexpressing lineage-defining transcription factors (TFs). Especially, for the activation of myogenic program, early studies have shown the effectiveness of enforced expression of TFs associated with myogenic differentiation, such as PAX7 and MYOD1. However, the efficiency of direct differentiation was rather low, most likely due to chromatin features unique to hPSCs, which hinder the access of TFs to genes involved in muscle differentiation. Indeed, recent studies have demonstrated that ectopic expression of epigenetic-modifying factors such as a histone demethylase and an ATP-dependent remodeling factor significantly enhances myogenic differentiation from hPSCs. In this article, we review the recent progress for in vitro generation of skeletal muscles from hPSCs through forced epigenetic and transcriptional manipulation.</p>

  • Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells

    Akiyama Tomohiko, Wakabayashi Shunichi, Soma Atsumi, Sato Saeko, Nakatake Yuhki, Oda Mayumi, Murakami Miyako, Sakota Miki, Chikazawa-Nohtomi Nana, Ko Shigeru B H, Ko Minoru S H

    Development (Cambridge) 143 （ 20 ） 3674 - 3685 2016年10月

    ISSN  0950-1991

    　概要を見る

    <p>Harnessing epigenetic regulation is crucial for the efficient and proper differentiation of pluripotent stem cells (PSCs) into desired cell types. Histone H3 lysine 27 trimethylation (H3K27me3) functions as a barrier against cell differentiation through the suppression of developmental gene expression in PSCs. Here, we have generated human PSC (hPSC) lines in which genome-wide reduction of H3K27me3 can be induced by ectopic expression of the catalytic domain of the histone demethylase JMJD3 (called JMJD3c). We found that transient, forced demethylation of H3K27me3 alone triggers the upregulation of mesoendodermal genes, even when the culture conditions for the hPSCs are not changed. Furthermore, transient and forced expression of JMJD3c followed by the forced expression of lineage-defining transcription factors enabled the hPSCs to activate tissue-specific genes directly. We have also shown that the introduction of JMJD3c facilitates the differentiation of hPSCs into functional hepatic cells and skeletal muscle cells. These results suggest the utility of the direct manipulation of epigenomes for generating desired cell types from hPSCs for cell transplantation therapy and platforms for drug screenings.</p>

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 組織幹細胞の維持・若返りを可能にする新規分子メカニズム

    2017年04月
    -
    2020年03月

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

  • ES細胞における減数分裂関連因子の機能解析

    2015年04月
    -
    2017年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 洪　実, 挑戦的萌芽研究, 補助金,  研究代表者

    　研究概要を見る

    Zscan4はマウス着床前胚2細胞期に発現することが知られており、zygotic遺伝子群の活性化と減数分裂関連遺伝子の異所的な発現を特徴とする。本研究では内在性Zscan4c遺伝子座にGFPをノックインしたES細胞およびマウスを作製して、内在性Zscan4の発現パターンの解析を行った。その結果、ES細胞内の内在性Zscan4cは全Zscan4陽性細胞のうち約30%であることが判明した。またmeiotic prophaseの後期に相当するGV oocyteおよびパキテン期の精母細胞でZscan4の発現が見られることが判明した。

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担当授業科目 【 表示 ／ 非表示 】

  • システム生物学

    2022年度

  • 再生医学

    2022年度

  • ＭＣＢ

    2022年度

  • システム医学演習

    2021年度

  • システム医学実習

    2021年度

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