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。
研究人员发现，初始hesc中自分泌成纤维细胞生长因子2（fgf2）信号的不完全阻断会在x染色体和多能状态中产生明显的异质性。研究人员获得了具有双重等位基因xist表达和高水平tfcp2l1的纯合xaxa初始hesc，其转录组和x染色体状态类似于人着床前的成骨细胞。这些细胞从初始到活化后，会随机启动xci，并且会获得xci之前和之后的hesc。研究人员在进一步xci前活化的hesc分化过程中，观察到了随机xci。
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总之，这些发现能够实现均质的初始hesc产生，并建立了研究人类xci的平台。
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附：英文原文
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
issuevolume: 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 statuswe 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 obtainedwe 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: 101016jstem202006002