MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux

被引：124

作者：

Cliff, Timothy S. ^{[1
,2
]}

Wu, Tianming ^{[1
,2
]}

Boward, Benjamin R. ^{[1
,2
]}

Yin, Amelia ^{[1
,2
]}

Yin, Hang ^{[1
,2
]}

Glushka, John N. ^{[1
,3
]}

Prestegaard, James H. ^{[1
,3
]}

Dalton, Stephen ^{[1
,2
]}

机构：

[1] Univ Georgia, Dept Biochem & Mol Biol, 500 DW Brooks Dr, Athens, GA 30602 USA

[2] Univ Georgia, Ctr Mol Med, 500 DW Brooks Dr, Athens, GA 30602 USA

[3] Univ Georgia, Complex Carbohydrate Res Ctr, 315 Riverbend Rd, Athens, GA 30602 USA

来源：

CELL STEM CELL | 2017年 / 21卷 / 04期

关键词：

EMBRYONIC STEM; EXPRESSION ANALYSIS; HUMAN ES; GLYCOLYTIC METABOLISM; SELF-RENEWAL; DIFFERENTIATION; CANCER; SWITCH; MAINTENANCE; GENE;

D O I：

10.1016/j.stem.2017.08.018

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

As human pluripotent stem cells (hPSCs) exit pluripotency, they are thought to switch from a glycolytic mode of energy generation to one more dependent on oxidative phosphorylation. Here we show that, although metabolic switching occurs during early mesoderm and endoderm differentiation, high glycolytic flux is maintained and, in fact, essential during early ectoderm specification. The elevated glycolysis observed in hPSCs requires elevated MYC/MYCN activity. Metabolic switching during endodermal and mesodermal differentiation coincides with a reduction in MYC/MYCN and can be reversed by ectopically restoring MYC activity. During early ectodermal differentiation, sustained MYCN activity maintains the transcription of "switch'' genes that are rate-limiting for metabolic activity and lineage commitment. Our work, therefore, shows that metabolic switching is lineage-specific and not a required step for exit of pluripotency in hPSCs and identifies MYC and MYCN as developmental regulators that couple metabolism to pluripotency and cell fate determination.

引用

页码：502 / +

页数：24

共 62 条

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Miz1 is required for early embryonic development during gastrulation [J].