EED is required for mouse primordial germ cell differentiation in the embryonic gonad

Matthew G Lowe; Ming-Ren Yen; Fei-Man Hsu; Linzi Hosohama; Zhongxun Hu; Tsotne Chitiashvili; Timothy J Hunt; Isaac Gorgy; Matthew Bernard; Sissy E Wamaitha; Pao-Yang Chen; Amander T Clark

doi:10.1016/j.devcel.2022.05.012

EED is required for mouse primordial germ cell differentiation in the embryonic gonad

Dev Cell. 2022 Jun 20;57(12):1482-1495.e5. doi: 10.1016/j.devcel.2022.05.012. Epub 2022 Jun 8.

Authors

Affiliations

¹ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA.
² Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
³ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA.
⁴ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
⁵ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.
⁶ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
⁷ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA. Electronic address: [email protected].

Abstract

Development of primordial germ cells (PGCs) is required for reproduction. During PGC development in mammals, major epigenetic remodeling occurs, which is hypothesized to establish an epigenetic landscape for sex-specific germ cell differentiation and gametogenesis. In order to address the role of embryonic ectoderm development (EED) and histone 3 lysine 27 trimethylation (H3K27me3) in this process, we created an EED conditional knockout mouse and show that EED is essential for regulating the timing of sex-specific PGC differentiation in both ovaries and testes, as well as X chromosome dosage decompensation in testes. Integrating chromatin and whole genome bisulfite sequencing of epiblast and PGCs, we identified a poised repressive signature of H3K27me3/DNA methylation that we propose is established in the epiblast where EED and DNMT1 interact. Thus, EED joins DNMT1 in regulating the timing of sex-specific PGC differentiation during the critical window when the gonadal niche cells specialize into an ovary or testis.

Keywords: DNMT1; EED; H3K27me3; PRC2; embryo; meiosis; ovary development; primordial germ cells; testis development.

MeSH terms

Animals
Cell Differentiation / genetics
DNA Methylation
Ectoderm / embryology
Female
Germ Cells* / metabolism
Gonads / metabolism
Histones* / genetics
Histones* / metabolism
Male
Mice
Polycomb Repressive Complex 2* / genetics
Polycomb Repressive Complex 2* / metabolism

Substances

Eed protein, mouse
Histones
Polycomb Repressive Complex 2

Abstract

MeSH terms

Substances

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