期刊
CELL RESEARCH
卷 22, 期 1, 页码 168-177出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2011.177
关键词
reprogramming; iPS cells; metabolome; stem cells; metabolism
类别
资金
- NIH [T32 CA009370, R24 EY017540-04, P30 MH062261- 10, P01 DA026146-02]
- Instituto de Salud Carlos III [CGCV-1335/07-3]
- California Institute of Regenerative Medicine [TR1-01219]
- CIRM [RB2-01530]
- Helmsley Charitable Trust
- Howard Hughes Medical Institute
- Fundacion Cellex
- G. Harold and Leila Y. Mathers Charitable Foundation
- Sanofi-Aventis
- CIBER
- TERCEL
- MICINN
- NATIONAL CANCER INSTITUTE [T32CA009370, P30CA014195] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R24EY017540] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL107442] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P30MH062261] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA026146] Funding Source: NIH RePORTER
Metabolism is vital to every aspect of cell function, yet the metabolome of induced pluripotent stem cells (iPSCs) remains largely unexplored. Here we report, using an untargeted metabolomics approach, that human iPSCs share a pluripotent metabolomic signature with embryonic stem cells (ESCs) that is distinct from their parental cells, and that is characterized by changes in metabolites involved in cellular respiration. Examination of cellular bioenergetics corroborated with our metabolomic analysis, and demonstrated that somatic cells convert from an oxidative state to a glycolytic state in pluripotency. Interestingly, the bioenergetics of various somatic cells correlated with their reprogramming efficiencies. We further identified metabolites that differ between iPSCs and ESCs, which revealed novel metabolic pathways that play a critical role in regulating somatic cell reprogramming. Our findings are the first to globally analyze the metabolome of iPSCs, and provide mechanistic insight into a new layer of regulation involved in inducing pluripotency, and in evaluating iPSC and ESC equivalence.
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