title: Transient activation of autophagy via Sox2-mediated suppression of mTOR is an important early step in reprogramming to pluripotency.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.forename: Pengyan
authors.initials: P
authors.lastname: Xia
authors.forename: Buqing
authors.initials: B
authors.lastname: Ye
authors.forename: Guanling
authors.initials: G
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Zusen
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D058570:TOR Serine-Threonine Kinases