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Cell Stem Cell. 2010 Sep 3;7(3):329-42. doi: 10.1016/j.stem.2010.06.024. Epub 2010 Aug 19.

Female human iPSCs retain an inactive X chromosome.

Author information

  • 1Department of Biological Chemistry, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90024, USA.

Abstract

Generating induced pluripotent stem cells (iPSCs) requires massive epigenome reorganization. It is unclear whether reprogramming of female human cells reactivates the inactive X chromosome (Xi), as in mouse. Here we establish that human (h)iPSCs derived from several female fibroblasts under standard culture conditions carry an Xi. Despite the lack of reactivation, the Xi undergoes defined chromatin changes, and expansion of hiPSCs can lead to partial loss of XIST RNA. These results indicate that hiPSCs are epigenetically dynamic and do not display a pristine state of X inactivation with two active Xs as found in some female human embryonic stem cell lines. Furthermore, whereas fibroblasts are mosaic for the Xi, hiPSCs are clonal. This nonrandom pattern of X chromosome inactivation in female hiPSCs, which is maintained upon differentiation, has critical implications for clinical applications and disease modeling, and could be exploited for a unique form of gene therapy for X-linked diseases.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID:
20727844
[PubMed - indexed for MEDLINE]
PMCID:
PMC2935700
Free PMC Article

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