Abstract
In mammals, X chromosome inactivation (XCI) is a process in which one of the two X chromosomes is silenced, following XIST expression. Mouse female pluripotent stem cells do not express Xist, and harbor two active X chromosomes. However, analysis of XCI in human embryonic stem cells (hESCs), mainly based on XIST expression, was not conclusive. Here, we studied XCI in hESCs by meta-analysis of the expression of the entire set of genes on the X chromosome in 21 female hESC lines. Thus, we could divide the ES cell lines into three categories: lines with no XCI, lines with full XCI, and lines with partial XCI. The partial inactivation of the X chromosome always involved the middle of the chromosome, surrounding the XIST transcription site. The status of XCI in some of the cell lines was validated by either allelic-specific expression or DNA methylation analysis. Interestingly, analysis of 10 female human-induced pluripotent stem cell (hiPSC) lines demonstrated similar heterogeneity in the inactivation of X chromosome and could also be classified into the same three categories detected in hESCs. Thus, we could show that in some hiPSC lines, the X chromosome was activated on reprogramming. Based on our analysis, we propose a model of the dynamics of XCI in pluripotent stem cells.
| Original language | American English |
|---|---|
| Pages (from-to) | 187-193 |
| Number of pages | 7 |
| Journal | Stem Cell Research |
| Volume | 6 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 2011 |
Bibliographical note
Funding Information:We thank Yoav Mayshar for help with the analysis and for stimulating discussions. We thank Yonatan Stelzer for valuable help with SNP and DNA methylation analysis, Uri Ben-David for his kind assistance with the expression profile analysis, and Dr. Danny Kitzberg for critically reading this manuscript. We also thank Juan-Carlos Biancotti for his help with the analysis of the allelic-specific expression and Tamar Golan-Lev for art work assistance. N.B. is the Herbert Cohn Chair in Cancer Research. This research was partially supported by funds from the Morasha-ISF (Grant 943/09). We gratefully acknowledge support for this project provided by a grant from the Legacy Heritage Fund.