Ko, Minoru



School of Medicine (Mita)


Professor Emeritus

Related Websites

External Links

Career 【 Display / hide

  • 1988.04

    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

  • 1991.08

    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

  • 1992.09

    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

  • 1997.09

    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)

  • 1998.09

    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

display all >>

Academic Background 【 Display / hide

  • 1980.04

    Keio University, School of Medicine

    University, Graduated

  • 1986.04

    Keio University, 医学研究科

    Graduate School, Withdrawal before completion, Doctoral course

Academic Degrees 【 Display / hide

  • 医学博士, Keio University, Dissertation, 1991.07

Licenses and Qualifications 【 Display / hide

  • 医師免許, 1986


Books 【 Display / hide

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

    Ko Minoru, McGraw-Hill, 2015

    Scope: Stem Cell Biology

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

    Ko Minoru, McGraw-Hill, 2011

    Scope: Stem Cell Biology

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

    Ko Minoru, McGraw-Hill, 2008

    Scope: Stem Cell Biology

  • Human Pluripotent Stem Cells

    Ko Minoru, BIOS Scientific Publishers, 2004

    Scope: Genomic approaches to stem cell biology

  • Mammalian Genomics

    Ko Minoru, CABI Publishing, 2004

    Scope: Regulation of genome activity and genetic networks in mammals

display all >>

Papers 【 Display / hide


    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 2017.08

    ISSN  1367-4803

     View Summary

    <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  2017.05

    ISSN  0006-291X

     View Summary

    <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 2017.02

    ISSN  2045-2322

     View Summary

    <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

     View Summary

    <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 2016.10

    ISSN  0950-1991

     View Summary

    <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>

display all >>

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

display all >>

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

  • 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


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

  • Functional analysis of meiosis-related factors in ES cells


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Exploratory Research, Principal investigator

     View Summary

    Zscan4 is known to be expressed in the 2 cell stage mouse embryos and is characterized by activation of the zygotic genes and ectopic expression of meiosis-related genes. In this study, ES cells and mice in which GFP was knocked-in at the endogenous Zscan4c locus were prepared, and the expression pattern of endogenous Zscan4 was analyzed. As a result, it was found that the endogenous Zscan4c in ES cells is about 30% of all Zscan4 positive cells. Expression of Zscan4 was observed in GV oocytes corresponding to late stage of meiotic prophase and spermatocytes at Pachytene stage.


Courses Taught 【 Display / hide











display all >>