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Germline development from human pluripotent stem cells toward disease modeling of infertility

  • Yohei Hayashi
    Correspondence
    Reprint requests: Yohei Hayashi, Ph.D., Gladstone Institute of Cardiovascular Disease, 1650 Owens St., San Francisco, CA 94158.
    Affiliations
    Gladstone Institute of Cardiovascular Disease, San Francisco, California
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  • Mitinori Saitou
    Affiliations
    Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST)/ Exploratory Research for Advanced Technology (ERATO), Kyoto, Japan

    Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan

    Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
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  • Shinya Yamanaka
    Affiliations
    Gladstone Institute of Cardiovascular Disease, San Francisco, California

    Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan

    Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
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      Infertility caused by the disruption or absence of germ cells (i.e., sperm or egg) is a major and largely incurable medical problem. In vitro disease modeling using normal human germline cells is required to better understand the precise molecular mechanisms of infertility and to develop drugs to treat this condition. Recent advances in the differentiation methods of embryonic stem cells (ESCs) provide new avenues to generate germ cells in vitro. Furthermore, the discovery that induced pluripotent stem cells (iPSCs) can be created from a patient's adult somatic cells by introducing the combinations of several transcription factors (e.g., OCT3/4, SOX2, KLF4, and MYC) enables us to generate new and powerful in vitro human disease models. In this review, we summarize recent advances in the development of human germ cells from in vivo and in vitro cultured ESCs/iPSCs. Based on these studies, we propose strategies to develop in vitro disease models of infertility using human ESCs/iPSCs. Then, we also discuss the challenges that need to be addressed to harness the full potential of these models. These models will enable us to understand the precise molecular pathologies of infertility and will aid in the development of new treatments.
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