近期发表在《自然—细胞生物学》上的一项研究重点揭示了人体配子是如何发育的。该研究得出的结论或有助了解女性卵巢内卵母细胞和男性睾丸内干细胞的发育,从而为今后在培养皿中尝试培养配子提供一个指引方向。
处在生育年龄的成年人中大约十分之一患有不育症,且大多数病因不明。尽管人类的生育年龄处于15岁到45岁之间,但人体配子产生的时间要比这更早一些。因此,这意味着成年人的生育问题或许是由胎儿时期配子前体成型问题导致的。
Amander Clark等人将人体配子前体——卵母细胞和精子——从受精后6到20周的胎儿体内分离出来,并记录下引发前体出现的各种早期活动,而在此之前,有关配子成型早期阶段的各种可用信息均来自于对小鼠的研究。通过借助某个细胞表面蛋白表达分离人体配子前体以及从全球范围分析其DNA、RNA和蛋白质的变化,研究人员鉴定出两种主要的发育阶段,其中一种已在小鼠研究中获得确认。(生物谷Bioon.com)
doi:10.1038/ncb2638
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The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitrodifferentiation
Sofia Gkountela, Ziwei Li, John J. Vincent, Kelvin X. Zhang, Angela Chen, Matteo Pellegrini& Amander T. Clark
The generation of research-quality, clinically relevant cell types in vitro from human pluripotent stem cells requires a detailed understanding of the equivalent human cell types. Here we analysed 134 human embryonic and fetal samples from 6 to 20 developmental weeks and identified the stages at which cKIT+ primordial germ cells (PGCs), the precursors of gametes, undergo whole-genome epigenetic reprogramming with global depletion of 5mC, H3K27me3 and H2A.Z, and the time at which imprint erasure is initiated and 5hmC is present. Using five alternative 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 the mechanisms necessary to pass human DNA from one generation to the next.