title: DEPTOR is a stemness factor that regulates pluripotency of embryonic stem cells.
abstract: The mammalian target of rapamycin (mTOR) pathway regulates stem cell regeneration and differentiation in response to growth factors, nutrients, cellular energetics, and various extrinsic stressors. Inhibition of mTOR activity has been shown to enhance the regenerative potential of pluripotent stem cells. DEPTOR is the only known endogenous inhibitor of all known cellular mTOR functions. We show that DEPTOR plays a key role in maintaining stem cell pluripotency by limiting mTOR activity in undifferentiated embryonic stem cells (ESCs). DEPTOR levels dramatically decrease with differentiation of mouse ESCs, and knockdown of DEPTOR is sufficient to promote ESC differentiation. A strong decrease in DEPTOR expression is also observed during human ESCs differentiation. Furthermore, reduction in DEPTOR level during differentiation is accompanied by a corresponding increase in mTOR complex 1 activity in mouse ESCs. Our data provide evidence that DEPTOR is a novel stemness factor that promotes pluripotency and self-renewal in ESCs by inhibiting mTOR signaling.
authors.affiliation: Buck Institute for Research on Aging, Novato, California 94945 and.
authors.forename: Pooja
authors.initials: P
authors.lastname: Agrawal
authors.affiliation: Buck Institute for Research on Aging, Novato, California 94945 and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Buck Institute for Research on Aging, Novato, California 94945 and.
authors.forename: Shereen
authors.initials: S
authors.lastname: Chew
authors.affiliation: Buck Institute for Research on Aging, Novato, California 94945 and; Department of Ophthalmology, University of Washington, Seattle, Washington 98104. Electronic address: dlamba@buckinstitute.org.
authors.forename: Deepak A
authors.initials: DA
authors.lastname: Lamba
authors.affiliation: Buck Institute for Research on Aging, Novato, California 94945 and.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hughes
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C484523:AKT1S1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C556139:DEPTOR protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Cell Differentiation; Cell Signaling; Embryonic Stem Cell; Mammalian Target of Rapamycin (mTOR); Neurogenesis