近期發(fā)表在《自然—細胞生物學》上的一項研究重點揭示了人體配子是如何發(fā)育的,。該研究得出的結(jié)論或有助了解女性卵巢內(nèi)卵母細胞和男性睪丸內(nèi)干細胞的發(fā)育，從而為今后在培養(yǎng)皿中嘗試培養(yǎng)配子提供一個指引方向,。
處在生育年齡的成年人中大約十分之一患有不育癥,，且大多數(shù)病因不明,。盡管人類的生育年齡處于15歲到45歲之間，但人體配子產(chǎn)生的時間要比這更早一些,。因此,，這意味著成年人的生育問題或許是由胎兒時期配子前體成型問題導致的。
Amander Clark等人將人體配子前體——卵母細胞和精子——從受精后6到20周的胎兒體內(nèi)分離出來,，并記錄下引發(fā)前體出現(xiàn)的各種早期活動,，而在此之前，有關配子成型早期階段的各種可用信息均來自于對小鼠的研究,。通過借助某個細胞表面蛋白表達分離人體配子前體以及從全球范圍分析其DNA,、RNA和蛋白質(zhì)的變化,，研究人員鑒定出兩種主要的發(fā)育階段，其中一種已在小鼠研究中獲得確認,。(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.
