Of Mice and Men: In Vivo and In Vitro Studies of Primordial Germ Cell Specification.

Of Mice and Men: In Vivo and In Vitro Studies of Primordial Germ Cell Specification.
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DOI:
10.1055/s-0037-1599085
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发表时间:
2017-03
影响因子:
2.7
通讯作者:
DeFalco T
DeFalco T
中科院分区:
医学4区
文献类型:
--
作者:
Kumar DL;DeFalco T

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小鼠原始生殖细胞(PGCs),精子和卵子的前体细胞,规范,涉及三个主要的分子事件:体细胞程序的抑制;重新获得多能性;和重编程到一个独特的表观遗传基态。小鼠模型中的基因敲除研究,沿着全球转录组分析,已经揭示了PGC特化所必需的关键信号通路和转录因子。从这些研究中获得的知识已被广泛用于开发不仅在小鼠中而且在人中的稳健的体外PGC诱导模型。这些模型,反过来,形成了详细了解的信号通路和表观遗传动力学在体内PGC规范和发展的基础。在培养中人类PGC特化的重述对于理解正常和疾病状态下人类生殖细胞发育的机制具有巨大意义,并且对于解决基于生殖细胞的不育原因具有意义。
Specification of mouse primordial germ cells (PGCs), the precursors of sperm and eggs, involves three major molecular events: repression of the somatic program; re-acquisition of pluripotency; and reprogramming to a unique epigenetic ground state. Gene knockout studies in mouse models, along with global transcriptome analyses, have revealed the key signaling pathways and transcription factors essential for PGC specification. Knowledge obtained from these studies has been utilized extensively to develop robust in vitro PGC induction models not only in mice but also in humans. These models have, in turn, formed the basis for a detailed understanding of the signaling pathways and epigenetic dynamics during in vivo PGC specification and development. Recapitulation of human PGC specification in culture is of tremendous significance for understanding the mechanisms of human germ cell development in normal and disease states and has implications for addressing germ-cell-based causes of infertility.