The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation.

The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation.
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DOI:
10.1038/ncb2638
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发表时间:
2013-01
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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--
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Generation of research quality, clinically relevant cell types in vitro from human pluripotent stem cells (hPSCs) requires detailed understanding of the equivalent human cell types. Here we analyzed 134 human embryonic and fetal samples from 6–20 developmental weeks and identified the stages in which cKIT+ primordial germ cells (PGCs), the precursors of gametes, undergo whole genome epigenetic reprogramming with global depletion of 5mC, H3K27me3, H2A.Z and the time where imprint erasure is initiated and 5hmC is present. Using five alternate in vitro differentiation strategies combined with single-cell microfluidic analysis and a bona fide human cKIT+ PGC signature, we show the stage of cKIT+ PGC formation in the first 16 days of differentiation. Taken together, our study creates a resource of human germ line ontogeny that is essential for future studies aimed at in vitro differentiation and unveiling mechanisms necessary to pass human DNA from one generation to the next.
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