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Development

DMRT1 drives the human germline forward

Nature Cell Biology volume 25, pages 1408–1410 (2023)Cite this article

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The molecular program of human germline commitment remains largely unknown. A new study delineates the multifaceted functions of DMRT1 in human germline development, particularly in the transition from early to late primordial germ cells.

Human germline development originates from the specification of primordial germ cells (PGCs) around 2 weeks after fertilization, followed by the migration of PGCs to the genital ridges at approximately 5 weeks, accompanied by epigenetic reprogramming. After a period of mitosis, male and female PGCs asynchronously enter the late stage at 9–11 weeks, with male PGCs transitioning to a mitotic quiescent state and female PGCs initiating meiosis in response to retinoic acid signalling1. Although the transcriptional and epigenetic landscapes of PGCs at different stages have been characterized in detail1,2,3, our understanding of the molecular programs that drive germ cell development is the tip of the iceberg. At present, human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells can be robustly induced into PGC-like cells (hPGCLCs), enabling researchers to determine the functions of EOMES, TFAP2C, SOX17, BLIMP1 (also known as PRDM1) and PRDM14 in PGC specification2,3,4,5,6,7,8. Nonetheless, the molecular mechanisms that facilitate these nascent PGCs stepping forward remain unknown. DMRT1 is a conserved sexual regulator in vertebrates, and its expression in Sertoli cells is indispensable for the maintenance of male sexual fate9. Concomitantly, it exhibits a long-duration expression in male germ cells from at least 4 weeks after fertilization until the onset of meiosis during puberty10, but its role in the human germline has not been determined. In this issue of Nature Cell Biology, Irie and Lee et al.11 use the modified in vitro gametogenesis system to investigate the role of DMRT1 in the human germline and show that DMRT1 regulates the sequential expression of stage-specific genes by directly binding to target genes and changing the epigenetic profile to drive PGC differentiation.

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Fig. 1: Schematic diagram of the molecular regulatory network of human germline development and the extensive role of DMRT1.

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Author notes

  1. These authors contributed equally: Yongjie Lu, Peng Yuan.

Authors and Affiliations

  1. State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China

    Yongjie Lu, Peng Yuan & Jie Qiao

Authors
  1. Yongjie Lu
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  2. Peng Yuan
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  3. Jie Qiao
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Correspondence to Jie Qiao.

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The authors declare no competing interests.

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Lu, Y., Yuan, P. & Qiao, J. DMRT1 drives the human germline forward. Nat Cell Biol 25, 1408–1410 (2023). https://doi.org/10.1038/s41556-023-01196-8

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