Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells
Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells
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DOI：
10.1074/jbc.m802763200
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发表时间：
2008-10-17
影响因子：
4.8
通讯作者：
Finkel, Toren
中科院分区：
文献类型：
--
作者：
Schieke, Stefan M.;Ma, Mingchao;Finkel, Toren
关于线粒体代谢在干细胞生物学中的作用知之甚少。在这里，我们证明，小鼠胚胎干细胞分选为低和高静息线粒体膜电位（Δ Psi L-m和Δ Psi H-m）是无法区分的形态和多能性标志物的表达，而代谢率显着不同。有趣的是，Delta Psi L-m细胞在体外中胚层分化方面是高效的，但在体内不能有效地形成畸胎瘤，而Delta Psi H-m细胞以相反的方式表现。我们进一步证明，Δ Psi（m）反映了雷帕霉素（mTOR）激活的总体哺乳动物靶点的程度，并且（mTOR）抑制剂雷帕霉素降低代谢率，增强分化，并抑制具有高代谢率的小鼠胚胎干细胞的肿瘤形成。综上所述，我们的研究结果表明内在代谢参数和干细胞命运之间的耦合，可能形成新的富集策略和治疗选择的基础。
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 L-m and Delta Psi H-m) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, Delta Psi L-m cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas Delta Psi H-m 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.