Male fetal germ cell differentiation involves complex repression of the regulatory network controlling pluripotency

Patrick Western, Jocelyn van den Bergen, Denise Miles, Andrew Sinclair

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Mammalian germ cells are derived from the pluripotent epiblast and share features with pluripotent stem cells, including the expression of key genes that regulate developmental potency. The core genes Oct4, Sox2, and Nanog that regulate pluripotency in stem cells also perform important roles in regulating germ cell development and potentially in occurrence of germ line tumors in humans. Despite this, our understanding of the regulation of these genes during germ cell development remains limited. In this study we examine the regulation of pluripotency in the mouse fetal germ line. We show that male-specific methylation occurs in key functional elements of the Nanog and Sox2 promoters, and these genes are suppressed during early male germ cell differentiation. Furthermore, Oct4 translation is suppressed post-transcriptionally as germ cells differentiate down the male lineage and enter mitotic arrest. Combined, our data strongly support the conclusion that repression of the core machinery regulating pluripotency is a robust and early event involved in the differentiation of the male germ cell lineage. We hypothesize that active repression of pluripotency is required for fetal male germ cell differentiation and that failure of this mechanism may render germ cells susceptible to tumor formation.
Original languageEnglish
Pages (from-to)3026 - 3035
Number of pages10
JournalThe FASEB Journal
Issue number8
Publication statusPublished - 2010
Externally publishedYes

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