期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 3, 页码 348-358出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.072272
关键词
Mitochondria; Pluripotency; Embryonic stem cells; Neural stem cells; Differentiation; Secretion
类别
资金
- California Institute for Regenerative Medicine [CL1-00501-1]
- Larry L. Hillblom Foundation
- laboratory of Dale E. Bredesen [RS1-00163-1]
- National Institutes of Health [PL1 AG032118, P01 AG025901, P30 AG025708, R01 AG033542]
- W. M. Keck Foundation
- The Ellison Medical Foundation [AG-SS-2288-09]
Here, we have investigated mitochondrial biology and energy metabolism in human embryonic stem cells (hESCs) and hESC-derived neural stem cells (NSCs). Although stem cells collectively in vivo might be expected to rely primarily on anaerobic glycolysis for ATP supply, to minimise production of reactive oxygen species, we show that in vitro this is not so: hESCs generate an estimated 77% of their ATP through oxidative phosphorylation. Upon differentiation of hESCs into NSCs, oxidative phosphorylation declines both in absolute rate and in importance relative to glycolysis. A bias towards ATP supply from oxidative phosphorylation in hESCs is consistent with the expression levels of the mitochondrial gene regulators peroxisome-proliferator-activated receptor g coactivator (PGC)-1 alpha, PGC-1. and receptor-interacting protein 140 (RIP140) in hESCs when compared with a panel of differentiated cell types. Analysis of the ATP demand showed that the slower ATP turnover in NSCs was associated with a slower rate of most energy-demanding processes but occurred without a reduction in the cellular growth rate. This mismatch is probably explained by a higher rate of macromolecule secretion in hESCs, on the basis of evidence from electron microscopy and an analysis of conditioned media. Taken together, our developmental model provides an understanding of the metabolic transition from hESCs to more quiescent somatic cell types, and supports important roles for mitochondria and secretion in hESC biology.
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