Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells

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Abstract

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. Bar et al. perform a large-scale analysis of X chromosome inactivation (XCI) in over 700 samples of human pluripotent stem cells (PSCs). Erosion of XCI involves stable silencing of XIST and partial overexpression of distal X-linked genes and is prevalent in embryonic stem cells, but not in most induced PSCs.

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Bar, S., Seaton, L. R., Weissbein, U., Eldar-Geva, T., & Benvenisty, N. (2019). Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells. Cell Reports, 27(1), 20-29.e3. https://doi.org/10.1016/j.celrep.2019.03.019

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