Transient activation of autophagy via Sox2-mediated suppression of mTOR is an important early step in reprogramming to pluripotency

Cell Stem Cell. 2013 Nov 7;13(5):617-25. doi: 10.1016/j.stem.2013.10.005.


Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we show that autophagy is required for reprogramming of somatic cells to form induced pluripotent stem cells (iPSCs). Our data indicate that mammalian target of rapamycin (mTOR) is downregulated by Sox2 at an early stage of iPSC generation and that this transient downregulation of mTOR is required for reprogramming to take place. In the absence of Sox2, mTOR remains at a high level and inhibits autophagy. Mechanistically, Sox2 binds to a repressive region on the mTOR promoter and recruits the NuRD complex to mediate transcriptional repression. We also detected enhanced autophagy at the four- to eight-cell stage of embryonic development, and a similar Sox2 and mTOR-mediated regulatory pathway seems to operate in this context as well. Thus, our findings reveal Sox2-dependent temporal regulation of autophagy as a key step in cellular reprogramming processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology*
  • Autophagy-Related Protein 5
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / physiology
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological
  • Promoter Regions, Genetic / genetics
  • SOXB1 Transcription Factors / chemistry
  • SOXB1 Transcription Factors / metabolism*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*


  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Microtubule-Associated Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • TOR Serine-Threonine Kinases