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Cell Rep. 2019 Apr 2;27(1):20-29.e3. doi: 10.1016/j.celrep.2019.03.019.

Global Characterization of X Chromosome Inactivation in Human Pluripotent Stem Cells.

Author information

1
The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
2
IVF Unit, Division of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel; The Hebrew University School of Medicine, Jerusalem, Israel.
3
The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. Electronic address: nissimb@mail.huji.ac.il.

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.

KEYWORDS:

X inactivation; XIST; human embryonic stem cells; human induced pluripotent stem cells

PMID:
30943402
DOI:
10.1016/j.celrep.2019.03.019
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