期刊
CELL
卷 146, 期 4, 页码 519-532出版社
CELL PRESS
DOI: 10.1016/j.cell.2011.06.052
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- JST-CREST
- Takeda Science Foundation
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [20062011, 21770251, 19061001, 21677003, 09J05542] Funding Source: KAKEN
The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-beta 3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.
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