Overcoming Autocrine FGF Signaling-Induced Heterogeneity in Naive Human ESCs Enables Modeling of Random X Chromosome Inactivation
收藏干细胞与再生医学数据中心2022-05-21 更新2024-03-06 收录
下载链接：
http://data.iscr.ac.cn/Article?id=f5ecc3dcce08f727efe8d327b193c9f5
下载链接
链接失效反馈官方服务：
资源简介：
Primed and naive human embryonic stem cells (hESCs) do not fully recapitulate the X chromosome status observed in human preimplantation epiblast and fail to initiate random X chromosome inactivation (XCI) upon differentiation. Therefore, an ideal system for studying XCI during early human development is yet to be established. We show that incomplete blocking of autocrine fibroblast growth factor 2 (FGF2) signaling in 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 states are similar to human preimplantation epiblast. Random XCI was initiated upon naive-to-primed conversion 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 primed hESCs. Together, these findings enable derivation of homogeneous naive hESCs and establish a powerful platform to study human XCI.
提供机构：
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology
创建时间：
2022-05-21
