이선민 (Henry Wellcome Building of Cancer and Developmental Biology, 건국대학교) | 한빛사논문 > 한빛사

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조회734

이선민Sun-Min Lee

Henry Wellcome Building of Cancer and Developmental Biology, 건국대학교

Nat. Cell Biol., Sep 14 2023 | https://doi.org/10.1038/s41556-023-01224-7 DMRT1 regulates human germline commitment.

Naoko Irie ^1,2,11,12 , Sun-Min Lee^1,3,11, Valentina Lorenzi ^4,5, Haiqi Xu⁶, Jinfeng Chen⁶, Masato Inoue⁶, Toshihiro Kobayashi^7,8, Carmen Sancho-Serra⁴, Elena Drousioti¹, Sabine Dietmann⁹, Roser Vento-Tormo ⁴, Chun-Xiao Song⁶ & M. Azim Surani^1,10,12

¹Wellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK.

²Metabolic Systems Laboratory, Live Imaging Center, Central Institute for Experimental Animals, Kanagawa, Japan.

³Department of Physics, Konkuk University, Seoul, Republic of Korea.

⁴Wellcome Sanger Institute, Cambridge, UK.

⁵European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK.

⁶Ludwig Institute for Cancer Research and Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

⁷Division of Mammalian Embryology, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

⁸Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Aichi, Japan.

⁹Department of Developmental Biology and Institute for Informatics, Washington University School of Medicine, St. Louis, MO, USA.

¹⁰Physiology, Development and Neuroscience Department, University of Cambridge, Cambridge, UK.

¹¹These authors contributed equally: Naoko Irie, Sun-Min Lee.

¹²These authors jointly supervised this work: Naoko Irie, M. Azim Surani.

Corresponding authors : Correspondence to Naoko Irie or M. Azim Surani.

Abstract

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-27)
연구진국내+국외 연구진
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