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In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells

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  • Dajung Jung

    (Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University)

  • Jie Xiong

    (Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University)

  • Min Ye

    (Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University)

  • Xunsi Qin

    (Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University)

  • Lin Li

    (Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University
    Tsinghua-Peking-NIBS Center for Life Sciences, School of Medicine, Tsinghua University)

  • Shunfeng Cheng

    (Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University)

  • Mengyuan Luo

    (Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University)

  • Jia Peng

    (Discovery, Baylor College of Medicine
    Discovery, Baylor College of Medicine)

  • Ji Dong

    (College of Life Sciences, Third Hospital, Peking University)

  • Fuchou Tang

    (College of Life Sciences, Third Hospital, Peking University)

  • Wei Shen

    (Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University)

  • Martin M. Matzuk

    (Discovery, Baylor College of Medicine
    Discovery, Baylor College of Medicine
    Discovery, Baylor College of Medicine
    Discovery, Baylor College of Medicine)

  • Kehkooi Kee

    (Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University
    Tsinghua-Peking-NIBS Center for Life Sciences, School of Medicine, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University)

Abstract

Understanding the unique mechanisms of human oogenesis necessitates the development of an in vitro system of stem cell differentiation into oocytes. Specialized cell types and organoids have been derived from human pluripotent stem cells in vitro, but generating a human ovarian follicle remains a challenge. Here we report that human embryonic stem cells can be induced to differentiate into ovarian follicle-like cells (FLCs) in vitro. First, we find that two RNA-binding proteins specifically expressed in germ cells, DAZL and BOULE, regulate the exit from pluripotency and entry into meiosis. By expressing DAZL and BOULE with recombinant human GDF9 and BMP15, these meiotic germ cells are further induced to form ovarian FLCs, including oocytes and granulosa cells. This robust in vitro differentiation system will allow the study of the unique molecular mechanisms underlying human pluripotent stem cell differentiation into late primordial germ cells, meiotic germ cells and ovarian follicles.

Suggested Citation

  • Dajung Jung & Jie Xiong & Min Ye & Xunsi Qin & Lin Li & Shunfeng Cheng & Mengyuan Luo & Jia Peng & Ji Dong & Fuchou Tang & Wei Shen & Martin M. Matzuk & Kehkooi Kee, 2017. "In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15680
    DOI: 10.1038/ncomms15680
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    Cited by:

    1. Wenqi Hu & Haitao Zeng & Yanan Shi & Chuanchuan Zhou & Jiana Huang & Lei Jia & Siqi Xu & Xiaoyu Feng & Yanyan Zeng & Tuanlin Xiong & Wenze Huang & Peng Sun & Yajie Chang & Tingting Li & Cong Fang & Ke, 2022. "Single-cell transcriptome and translatome dual-omics reveals potential mechanisms of human oocyte maturation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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