DMRT1 regulates human germline commitment

Naoko Irie; Sun Min Lee; Valentina Lorenzi; Haiqi Xu; Jinfeng Chen; Masato Inoue; Toshihiro Kobayashi; Carmen Sancho-Serra; Elena Drousioti; Sabine Dietmann; Roser Vento-Tormo; Chun Xiao Song; M. Azim Surani

doi:10.1038/s41556-023-01224-7

DMRT1 regulates human germline commitment

Naoko Irie
, Sun Min Lee
, Valentina Lorenzi
, Haiqi Xu
, Jinfeng Chen
, Masato Inoue
, Toshihiro Kobayashi
, Carmen Sancho-Serra
, Elena Drousioti
, Sabine Dietmann
, Roser Vento-Tormo
, Chun Xiao Song
, M. Azim Surani

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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.

Original language	English
Pages (from-to)	1439-1452
Number of pages	14
Journal	Nature Cell Biology
Volume	25
Issue number	10
DOIs	https://doi.org/10.1038/s41556-023-01224-7
State	Published - Oct 2023

Access to Document

10.1038/s41556-023-01224-7

Cite this

@article{a828ffef3bc84c038aa9c2d1294dedc0,

title = "DMRT1 regulates human germline commitment",

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.",

author = "Naoko Irie and Lee, \{Sun Min\} and Valentina Lorenzi and Haiqi Xu and Jinfeng Chen and Masato Inoue and Toshihiro Kobayashi and Carmen Sancho-Serra and Elena Drousioti and Sabine Dietmann and Roser Vento-Tormo and Song, \{Chun Xiao\} and Surani, \{M. Azim\}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = oct,

doi = "10.1038/s41556-023-01224-7",

language = "English",

volume = "25",

pages = "1439--1452",

journal = "Nature Cell Biology",

issn = "1465-7392",

number = "10",

}

TY - JOUR

T1 - DMRT1 regulates human germline commitment

AU - Irie, Naoko

AU - Lee, Sun Min

AU - Lorenzi, Valentina

AU - Xu, Haiqi

AU - Chen, Jinfeng

AU - Inoue, Masato

AU - Kobayashi, Toshihiro

AU - Sancho-Serra, Carmen

AU - Drousioti, Elena

AU - Dietmann, Sabine

AU - Vento-Tormo, Roser

AU - Song, Chun Xiao

AU - Surani, M. Azim

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85170835182

U2 - 10.1038/s41556-023-01224-7

DO - 10.1038/s41556-023-01224-7

M3 - Article

C2 - 37709822

AN - SCOPUS:85170835182

SN - 1465-7392

VL - 25

SP - 1439

EP - 1452

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 10

ER -

DMRT1 regulates human germline commitment

Abstract

Access to Document

Other files and links

Fingerprint

Cite this