title: Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells.
abstract: Relatively little is known regarding the role of mitochondrial metabolism in stem cell biology. Here we demonstrate that mouse embryonic stem cells sorted for low and high resting mitochondrial membrane potential (DeltaPsi(m)L and DeltaPsi(m)H) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, DeltaPsi(m)L cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas DeltaPsi(m)H cells behave in the opposite fashion. We further demonstrate that DeltaPsi(m) reflects the degree of overall mammalian target of rapamycin (mTOR) activation and that the mTOR inhibitor rapamycin reduces metabolic rate, augments differentiation, and inhibits tumor formation of the mouse embryonic stem cells with a high metabolic rate. Taken together, our results suggest a coupling between intrinsic metabolic parameters and stem cell fate that might form a basis for novel enrichment strategies and therapeutic options.
authors: Translational Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Stefan M
authors: SM
authors: Schieke
authors: Mingchao
authors: M
authors: Ma
authors: Liu
authors: L
authors: Cao
authors: J Philip
authors: JP
authors: McCoy
authors: Chengyu
authors: C
authors: Liu
authors: Nancy F
authors: NF
authors: Hensel
authors: A John
authors: AJ
authors: Barrett
authors: Manfred
authors: M
authors: Boehm
authors: Toren
authors: T
authors: Finkel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D016513:Mice, SCID; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D011494:Protein Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D013724:Teratoma / Q000378:metabolism / Q000473:pathology*
chemical_list: D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D010100:Oxygen