小柯机器人

中国科学院动物研究所王皓毅研究小组建立了随机X染色体失活的初始人类胚胎干细胞平台。这一研究成果于2020年7月15日在线发表在《细胞—干细胞》上。

据研究人员介绍，活化和初始的人类胚胎干细胞（hESC）不能完全概括在人类着床前成骨细胞中观察到的X染色体状态，并且在分化后无法启动随机X染色体失活（XCI）。因此，在人类早期发育中研究XCI的理想系统尚未建立。

Title: Overcoming Autocrine FGF Signaling-Induced Heterogeneity in Naive Human ESCs Enables Modeling of Random X Chromosome Inactivation

Author: Chenrui An, Guihai Feng, Jixiang Zhang, Shiwei Cao, Ying Wang, Nannan Wang, Falong Lu, Qi Zhou, Haoyi Wang

Issue&Volume: 2020-07-15

Abstract: Primed and naive human embryonic stem cells (hESCs) do not fully recapitulate theX chromosome status observed in human preimplantation epiblast and fail to initiaterandom X chromosome inactivation (XCI) upon differentiation. Therefore, an ideal systemfor studying XCI during early human development is yet to be established. We showthat incomplete blocking of autocrine fibroblast growth factor 2 (FGF2) signalingin naive hESCs drives significant heterogeneity in X chromosome and pluripotency status.We derived homozygous XaXa naive hESCs with dual allelic XIST expression and high levels of TFCP2L1, whose transcriptome and X chromosome statesare similar to human preimplantation epiblast. Random XCI was initiated upon naive-to-primedconversion of these cells, and both pre- and post-XCI primed hESCs were obtained.We observed random XCI in all cells upon further differentiation of pre-XCI primedhESCs. Together, these findings enable derivation of homogeneous naive hESCs and establisha powerful platform to study human XCI.

DOI: 10.1016/j.stem.2020.06.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30269-1

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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