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

The Journal of Biological Chemistry
Stefan M SchiekeToren Finkel

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.

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Citations

Dec 19, 2012·Journal of Cardiovascular Translational Research·Clifford D L FolmesAndre Terzic
Jul 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Toren Finkel, Paul M Hwang
Jul 16, 2010·Stem Cells and Development·Xiaoyan XieJoseph C Wu
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Feb 20, 2013·Journal of Cell Science·Victoria A RafalskiAnne Brunet
Mar 14, 2012·PLoS Computational Biology·Iain G JohnstonNick S Jones
Nov 23, 2011·Biomarkers in Medicine·Clifford D L FolmesAndre Terzic
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May 30, 2013·Development·Ng Shyh-ChangLewis C Cantley
Feb 13, 2016·Seminars in Cell & Developmental Biology·Clifford D L Folmes, Andre Terzic
Dec 18, 2015·Cell Metabolism·Madhusudhanan SukumarNicholas P Restifo
Feb 24, 2016·International Journal of Molecular Sciences·Chenxia HuLanjuan Li
Jan 22, 2013·Biochemical and Biophysical Research Communications·Wenbo LiuXingguo Liu
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May 3, 2012·Annals of the New York Academy of Sciences·Clifford D L FolmesAndre Terzic

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