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通过单细胞分析揭示猪原肠胚前胚胎中的多能性和 X 染色体动态。

Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis.

机构信息

School of Biosciences, University of Nottingham, Sutton Bonington Campus, Nottingham, LE12 5RD, UK.

Animal Reproduction Department, National Institute for Agricultural and Food Research and Technology, 28040, Madrid, Spain.

出版信息

Nat Commun. 2019 Jan 30;10(1):500. doi: 10.1038/s41467-019-08387-8.

Abstract

High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are largely inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and of epiblast and hypoblast in late blastocysts. We show that following an emergent short naive pluripotent signature in early embryos, there is a protracted appearance of a primed signature in advanced embryonic stages. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.

摘要

近年来,高分辨率的分子程序已经描绘出了哺乳动物胚胎发生的细胞基础。类似的人类胚胎分析仅限于植入前阶段,因为早期的植入后胚胎基本上无法获得。尽管如此,我们之前已经提出了猪和人类早期发育的保守原则。为了进一步深入了解多能状态和谱系分化,我们在单细胞分辨率下分析了猪胚胎。在这里,我们显示了早期囊胚中内细胞团和滋养外胚层的逐渐分离,以及晚期囊胚中胚外和下胚层的分离。我们发现,在早期胚胎中出现短暂的原始多能特征后,在晚期胚胎阶段会出现一个延长的起始特征。雌性中 X 染色体的剂量补偿是通过晚期外胚层中的 X 染色体失活来实现的。详细的人与猪比较是理解早期人类发育的基础,也是进一步研究猪种间嵌合体中人类多能干细胞分化的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebef/6353908/f13a57070914/41467_2019_8387_Fig1_HTML.jpg

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