The THO complex regulates pluripotency gene mRNA export and controls embryonic stem cell self-renewal and somatic cell reprogramming

Cell Stem Cell. 2013 Dec 5;13(6):676-90. doi: 10.1016/j.stem.2013.10.008.


Embryonic stem cell (ESC) self-renewal and differentiation are governed by a broad-ranging regulatory network. Although the transcriptional regulatory mechanisms involved have been investigated extensively, posttranscriptional regulation is still poorly understood. Here we describe a critical role of the THO complex in ESC self-renewal and differentiation. We show that THO preferentially interacts with pluripotency gene transcripts through Thoc5 and is required for self-renewal at least in part by regulating their export and expression. During differentiation, THO loses its interaction with those transcripts due to reduced Thoc5 expression, leading to decreased expression of pluripotency proteins that facilitates exit from self-renewal. THO is also important for the establishment of pluripotency, because its depletion inhibits somatic cell reprogramming and blastocyst development. Together, our data indicate that THO regulates pluripotency gene mRNA export to control ESC self-renewal and differentiation, and therefore uncover a role for this aspect of posttranscriptional regulation in stem cell fate specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Blastocyst / metabolism
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Proliferation
  • Cellular Reprogramming / genetics*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Mice
  • Models, Biological
  • Multiprotein Complexes / metabolism*
  • Pluripotent Stem Cells / metabolism*
  • Protein Binding / genetics
  • RNA Transport / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Multiprotein Complexes
  • RNA, Messenger

Associated data

  • GEO/GSE48436
  • GEO/GSE51496