Journal
CELL
Volume 160, Issue 1-2, Pages 253-268Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.12.013
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Funding
- JSPS
- BIRAX (the Britain Israel Research and Academic Exchange Partnership) initiative
- ERC [StG-2011-281906]
- Helmsley Charitable Trust
- ISF (Bikura, Morasha, ICORE)
- ICRF
- Abisch Frenkel Foundation
- Fritz Thyssen Stiftung
- Erica and Robert Drake
- Benoziyo Endowment fund
- Flight Attendant Medical Research Institute (FAMRI)
- New York Stem Cell Foundation
- Croucher Foundation and Cambridge Trust
- HFSP
- Wellcome Trust
- The British Council [15BX12ASJH] Funding Source: researchfish
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Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.
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