Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells
Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells
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DOI：
10.1016/j.celrep.2019.03.019
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发表时间：
2019-04-02
期刊：
影响因子：
8.8
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
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作者：
Bar, Shiran;Seaton, Lev Roz;Benvenisty, Nissim
雄性和雌性哺乳动物之间性染色体基因表达的剂量补偿是通过X染色体失活（XCI）实现的，其通过采用表观遗传修饰在早期胚胎发生期间随机沉默一条X染色体。据报道，人类多能干细胞（hPSC）呈现出不同的XCI状态，其根据长非编码RNA XIST的表达和X染色体沉默的程度而不同。为了获得对雌性hPSC中XCI的全面观点，我们在700多个RNA高通量测序样品中进行了表征不同XCI参数的大规模分析。我们的研究结果表明，大多数已发表的胚胎干细胞（ESC）和诱导的PSC（iPSC）样本之间的XCI状态存在差异。虽然大多数iPSC系保持无活性的X染色体，但ESC系倾向于沉默XIST的表达并上调远端染色体区域。我们的研究强调了hPSC中显著的表观遗传异质性，这可能对它们在研究和再生治疗中的应用产生影响。
Dosage compensation of sex-chromosome gene expression between male and female mammals is achieved via X chromosome inactivation (XCI) by employing epigenetic modifications to randomly silence one X chromosome during early embryogenesis. Human pluripotent stem cells (hPSCs) were reported to present various states of XCI that differ according to the expression of the long non-coding RNA XIST and the degree of X chromosome silencing. To obtain a comprehensive perspective on XCI in female hPSCs, we performed a large-scale analysis characterizing different XCI parameters in more than 700 RNA high-throughput sequencing samples. Our findings suggest differences in XCI status between most published samples of embryonic stem cells (ESCs) and induced PSCs (iPSCs). While the majority of iPSC lines maintain an inactive X chromosome, ESC lines tend to silence the expression of XIST and upregulate distal chromosomal regions. Our study highlights significant epigenetic heterogeneity within hPSCs, which may bear implications for their use in research and regenerative therapy.