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多能干细胞向生殖细胞分化和发育过程中的表观基因组调控。

Epigenome regulation during germ cell specification and development from pluripotent stem cells.

机构信息

Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

Curr Opin Genet Dev. 2018 Oct;52:57-64. doi: 10.1016/j.gde.2018.06.004. Epub 2018 Jun 13.

DOI:10.1016/j.gde.2018.06.004
PMID:29908427
Abstract

Germ cells undergo epigenome reprogramming for proper development of the next generation. The realization of germ cell derivation from human and mouse pluripotent stem cells offers unprecedented opportunity for investigation of germline development. Primordial germ cells reconstituted in vitro (PGC-like cells [PGCLCs]) show progressive dilution of genomic DNA methylation, tightly linked with chromatin remodeling, during their specification. PGCLCs can be further expanded by plane culture, allowing maintenance of the gene-expression profiles of early PGCs and continuance of the DNA methylation erasure, thereby establishing an epigenetic `blank slate'. PGCLCs undergo further epigenome regulation to acquire the male or female fates. These findings will provide a foundation for basic germ cell biology and for in-depth evaluations of in vitro gametogenesis.

摘要

生殖细胞经历表观基因组重编程,以实现下一代的正常发育。人类和小鼠多能干细胞来源的生殖细胞的实现,为生殖系发育的研究提供了前所未有的机会。体外重建的原始生殖细胞(PGC 样细胞[PGCLC])在其特化过程中表现出基因组 DNA 甲基化的逐渐稀释,与染色质重塑紧密相关。PGCLC 可以通过平面培养进一步扩增,从而维持早期 PGC 的基因表达谱,并继续进行 DNA 甲基化擦除,从而建立一个表观遗传的“空白石板”。PGCLC 进一步经历表观基因组调控,获得雄性或雌性命运。这些发现将为基础生殖细胞生物学和深入评估体外配子发生提供基础。

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