Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells Export

@article{citeulike:3400479, 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 ({Delta}{Psi}mL and {Delta}{Psi}mH) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, {Delta}{Psi}mL cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas {Delta}{Psi}mH cells behave in the opposite fashion. We further demonstrate that {Delta}{Psi}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. 10.1074/jbc.M802763200}, author = {Schieke, Stefan M. and Ma, Mingchao and Cao, Liu and Mccoy, Philip J. and Liu, Chengyu and Hensel, Nancy F. and Barrett, John A. and Boehm, Manfred and Finkel, Toren}, citeulike-article-id = {3400479}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M802763200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/283/42/28506}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18713735}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18713735}, day = {17}, doi = {10.1074/jbc.M802763200}, journal = {J. Biol. Chem.}, keywords = {differentiation, mitochondria}, month = {October}, number = {42}, pages = {28506--28512}, posted-at = {2008-10-13 13:52:07}, priority = {3}, title = {Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells}, url = {http://dx.doi.org/10.1074/jbc.M802763200}, volume = {283}, year = {2008} }

TY - JOUR ID - citeulike:3400479 L3 - citeulike-article-id:3400479 N2 - 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 ({Delta}{Psi}mL and {Delta}{Psi}mH) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, {Delta}{Psi}mL cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas {Delta}{Psi}mH cells behave in the opposite fashion. We further demonstrate that {Delta}{Psi}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. 10.1074/jbc.M802763200 IS - 42 JF - J. Biol. Chem. EP - 28512 TI - Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells VL - 283 SP - 28506 KW - differentiation KW - mitochondria AU - Schieke, Stefan AU - Ma, Mingchao AU - Cao, Liu AU - Mccoy, Philip AU - Liu, Chengyu AU - Hensel, Nancy AU - Barrett, John AU - Boehm, Manfred AU - Finkel, Toren PY - 2008/10/17/ UR - http://dx.doi.org/10.1074/jbc.M802763200 ER -