西亚试剂：Mitochondrial metabolism modulates differentiation and tera

Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells

Stefan M Schieke, Mingchao Ma, Liu Cao, J. Phillip McCoy . Jr, Chengyu Liu, Nancy F. Hensel, A. John Barrett, Manfed Boehm, and Toren Finkel

NIH-NHLBI-LMB, NIH, Bethesda, MD 20892

Relatively little is known regarding the role of mitochondrial metabolism in stem cell biology. Here we demonstrate that mouse embryonic stem cells (mES) sorted for low and high resting mitochondrial membrane potential (mL and mH) are indistinguishable morphologically and by the expression of pluripotency markers while markedly differing in metabolic rates. Interestingly, mL cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, while mH cells behave in the opposite fashion. We further demonstrate that m reflects the degree of overall mTOR activation and that the mTOR inhibitor rapamycin reduces metabolic rate, augments differentiation, and inhibits tumor formation of the mES cells with a high metabolic rate. Taken together, our results suggest a coupling between intrinsic metabolic parameters and stem cell fate which might form a basis for novel enrichment strategies and therapeutic options.

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