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

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Publication Year:
2022
Authors:
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
PubMed ID:
35679863
Funding Grants:
Public Summary:
The development of primordial germ cells (PGCs) is crucial for reproduction. These cells undergo significant changes in their epigenetic makeup during development, which are thought to set the stage for the differentiation of male and female germ cells. To understand the role of specific factors, in this process, researchers created mice with a conditionally modified EED gene. Their findings indicate that EED is essential for controlling the timing of sex-specific PGC differentiation in both male and female gonads. It also plays a role in balancing the number of X chromosomes in male gonads. By analyzing the epigenetic modifications in PGCs, they identified a pattern of H3K27me3 and DNA methylation that is established in the early embryo. This pattern is thought to be important for regulating when PGCs differentiate into male or female germ cells. In summary, EED works in conjunction with another factor, DNMT1, to control the timing of sex-specific PGC differentiation during a critical period when the gonadal cells are becoming ovaries or testes.
Scientific 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.