Reactivation of the inactive X chromosome and post-transcriptional reprogramming of Xist in iPSCs

J Cell Sci. 2015 Jan 1;128(1):81-7. doi: 10.1242/jcs.154294. Epub 2014 Nov 6.

Abstract

Direct reprogramming of somatic cells to pluripotent stem cells entails the obliteration of somatic cell memory and the reestablishment of epigenetic events. Induced pluripotent stem cells (iPSCs) have been created by reprogramming somatic cells through the transduction of reprogramming factors. During cell reprogramming, female somatic cells must overcome at least one more barrier than male somatic cells in order to enter a pluripotent state, as they must reactivate an inactive X chromosome (Xi). In this study, we investigated whether the sex of somatic cells affects reprogramming efficiency, differentiation potential and the post-transcriptional processing of Xist RNA after reprogramming. There were no differences between male and female iPSCs with respect to reprogramming efficiency or their differentiation potential in vivo. However, reactivating Xi took longer than reactivating pluripotency-related genes. We also found that direct reprogramming leads to gender-appropriate post-transcriptional reprogramming - like male embryonic stem cells (ESCs), male iPSCs expressed only the long Xist isoform, whereas female iPSCs, like female ESCs, expressed both the long and short isoforms.

Keywords: Oct4; Pluripotency; Reprogramming; Xist isoform; iPSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellular Reprogramming*
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • Sex Characteristics*
  • X Chromosome / genetics
  • X Chromosome / metabolism*
  • X Chromosome Inactivation*

Substances

  • RNA, Long Noncoding
  • XIST non-coding RNA