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Specification and epigenetic programming of the human germ line
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Journal Article
Specification and epigenetic programming of the human germ line
2016
Overview
Key Points
Regulation of pluripotency and early post-implantation embryonic development have diverged between humans and mice, which might affect the mechanism of primordial germ cell (PGC) specification.
Specification of human and mouse PGCs occurs in response to extrinsic signals, including bone morphogenetic protein 2 (BMP2) and BMP4.
Models of human PGC specification from pluripotent stem cells suggest that human PGCs originate from mesodermal precursors at the posterior epiblast during the onset of gastrulation, whereas mouse PGCs originate from the pre-gastrulation epiblast.
The gene regulatory network for PGC specification and maintenance in humans and mice has diverged. Notably, SRY-box 17 (SOX17), a key endoderm specifier, is critical for PGC specification in humans but not in mice.
PGCs undergo genome-wide DNA demethylation, which erases parental epigenetic memories and facilitates germ cell differentiation in humans and mice.
Repressive histone modifications might safeguard PGC genome stability during global DNA demethylation.
In early germline development, extra-embryonic signals trigger a regulatory network that induces the specification and subsequent epigenetic reprogramming of primordial germ cells, the precursors of sperm and eggs. Here, the authors review germline specification and reprogramming in humans, and discuss the crucial mechanistic differences between these processes in humans and mice.
Primordial germ cells (PGCs), the precursors of sperm and eggs, are established in perigastrulation-stage embryos in mammals. Signals from extra-embryonic tissues induce a unique gene regulatory network in germline-competent cells for PGC specification. This network also initiates comprehensive epigenome resetting, including global DNA demethylation and chromatin reorganization. Mouse germline development has been studied extensively, but the extent to which such knowledge applies to humans was unclear. Here, we review the latest advances in human PGC specification and epigenetic reprogramming. The overall developmental dynamics of human and mouse germline cells appear to be similar, but there are crucial mechanistic differences in PGC specification, reflecting divergence in the regulation of pluripotency and early development.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
