Human pluripotent stem cells with distinct X inactivation status show molecular and cellular differences controlled by the X-Linked ELK-1 gene

Tal Bruck, Ofra Yanuka, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Female human pluripotent stem cells show vast heterogeneity regarding the status of X chromosome inactivation. By comparing the gene expression profile of cells with two active X chromosomes (XaXa cells) to that of cells with only one active X chromosome (XaXi cells), a set of autosomal genes was shown to be overexpressed in the XaXa cells. Among these genes, we found significant enrichment for genes regulated by the X-linked transcription factor ELK-1. Comparison of the phenotype of XaXa and XaXi cells demonstrated differences in programmed cell death and differentiation, implying some growth disadvantage of the XaXa cells. Interestingly, ELK-1-overexpressing cells mimicked the phenotype of XaXa cells, whereas knockdown of ELK-1 with small hairpin RNA mimicked the phenotype of XaXi cells. When cultured at low oxygen levels, these cellular differences were considerably weakened. Our analysis implies a role of ELK-1 in the differences between pluripotent stem cells with distinct X chromosome inactivation statuses

Original languageAmerican English
Pages (from-to)262-270
Number of pages9
JournalCell Reports
Volume4
Issue number2
DOIs
StatePublished - 25 Jul 2013

Bibliographical note

Funding Information:
The authors wish to thank all members of the lab for their technical support and helpful discussions. In addition, we would like to thank Yonatan Stelzer and Daniel Ronen and Nadav Sharon for critical reading of this manuscript. We thank Tamar Golan-Lev for her assistance with the graphic design. N.B. is the Herbert Cohn Chair in Cancer Research. This research was supported by the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation (grant 1252/12) and the Centers of Excellence Legacy Heritage Biomedical Science Partnership (grant 1801/10).

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