DMRT1 regulates human germline commitment

被引：23

作者：

Irie, Naoko ^{[1
,2
]}

Lee, Sun-Min ^{[1
,3
]}

Lorenzi, Valentina ^{[4
,5
]}

Xu, Haiqi ^{[6
,7
]}

Chen, Jinfeng ^{[6
,7
]}

Inoue, Masato ^{[6
,7
]}

Kobayashi, Toshihiro ^{[8
,9
]}

Sancho-Serra, Carmen ^{[4
]}

Drousioti, Elena ^{[1
]}

Dietmann, Sabine ^{[10
,11
]}

Vento-Tormo, Roser ^{[4
]}

Song, Chun-Xiao ^{[6
,7
]}

Surani, M. Azim ^{[1
,12
]}

机构：

[1] Wellcome Trust Res Labs, Canc Res UK Gurdon Inst, Henry Wellcome Bldg Canc & Dev Biol, Cambridge, England

[2] Cent Inst Expt Anim, Live Imaging Ctr, Metab Syst Lab, Kawasaki, Kanagawa, Japan

[3] Konkuk Univ, Dept Phys, Seoul, South Korea

[4] Wellcome Sanger Inst, Cambridge, England

[5] European Bioinformat Inst, European Mol Biol Lab, Cambridge, England

[6] Univ Oxford, Ludwig Inst Canc Res, Oxford, England

[7] Univ Oxford, Target Discovery Inst, Nuffield Dept Med, Oxford, England

[8] Univ Tokyo, Inst Med Sci, Ctr Stem Cell Biol & Regenerat Med, Div Mammalian Embryol, Tokyo, Japan

[9] Natl Inst Physiol Sci, Ctr Genet Anal Behav, Okazaki, Aichi, Japan

[10] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA

[11] Washington Univ Sch Med, Inst Informat, St. Louis, MO USA

[12] Univ Cambridge, Physiol Dev & Neurosci Dept, Cambridge, England

来源：

NATURE CELL BIOLOGY | 2023年 / 25卷 / 10期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 新加坡国家研究基金会;

关键词：

DNA DEMETHYLATION DYNAMICS; PLURIPOTENT STEM-CELLS; RETINOIC ACID; GROWTH-FACTOR; MOUSE; EXPRESSION; METHYLATION; SEX; SPECIFICATION; ELEMENTS;

D O I：

10.1038/s41556-023-01224-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. Irie, Lee et al. report a role for DMRT1 in human germline development and show that induction of DMRT1 in primordial germ cell-like cells triggers germline commitment, but suppresses pluripotency genes, thus promoting the onset of gametogenesis.

引用

页码：1439 / +

页数：33

共 111 条

[1] Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids [J].