HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition

被引：436

作者：

Zhou, Wenyu ^{[2
,3
]}

Choi, Michael ^{[1
,3
]}

Margineantu, Daciana ^{[4
]}

Margaretha, Lilyana ^{[3
,5
]}

Hesson, Jennifer ^{[3
,6
]}

Cavanaugh, Christopher ^{[3
,6
]}

Blau, C. Anthony ^{[3
,7
]}

Horwitz, Marshall S. ^{[3
,8
]}

Hockenbery, David ^{[4
]}

Ware, Carol ^{[3
,6
]}

Ruohola-Baker, Hannele ^{[1
,2
,3
]}

机构：

[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[2] Univ Washington, H Ruohola Baker Dept Biol, Seattle, WA 98195 USA

[3] ISCRM, Seattle, WA USA

[4] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[5] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA

[6] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA

[7] Univ Washington, Div Hematol, Seattle, WA 98195 USA

[8] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

来源：

EMBO JOURNAL | 2012年 / 31卷 / 09期

基金：

美国国家卫生研究院;

关键词：

human embryonic stem cell; hypoxia-inducible factor 1 alpha; metabolism; mouse embryonic stem cell; mouse epiblast stem cell; EMBRYONIC STEM-CELLS; CARBONYL CYANIDE PHENYLHYDRAZONES; MITOCHONDRIAL BIOGENESIS; MOUSE EMBRYOS; IN-VIVO; OXIDATIVE PHOSPHORYLATION; GROUND-STATE; SELF-RENEWAL; DIFFERENTIATION; RESPIRATION;

D O I：

10.1038/emboj.2012.71

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The function of metabolic state in stemness is poorly understood. Mouse embryonic stem cells (ESC) and epiblast stem cells (EpiSC) are at distinct pluripotent states representing the inner cell mass (ICM) and epiblast embryos. Human embryonic stem cells (hESC) are similar to EpiSC stage. We now show a dramatic metabolic difference between these two stages. EpiSC/hESC are highly glycolytic, while ESC are bivalent in their energy production, dynamically switching from glycolysis to mitochondrial respiration on demand. Despite having a more developed and expanding mitochondrial content, EpiSC/hESC have low mitochondrial respiratory capacity due to low cytochrome c oxidase (COX) expression. Similarly, in vivo epiblasts suppress COX levels. These data reveal EpiSC/hESC functional similarity to the glycolytic phenotype in cancer (Warburg effect). We further show that hypoxia-inducible factor 1 alpha (HIF1 alpha) is sufficient to drive ESC to a glycolytic Activin/Nodal-dependent EpiSC-like stage. This metabolic switch during early stem-cell development may be deterministic. The EMBO Journal (2012) 31, 2103-2116. doi:10.1038/emboj.2012.71; Published online 23 March 2012

引用

页码：2103 / 2116

页数：14

共 60 条

[1] IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro [J].

Bendall, Sean C. ;

Stewart, Morag H. ;

Menendez, Pablo ;

George, Dustin ;

Vijayaragavan, Kausalia ;

Werbowetski-Ogilvie, Tamra ;

Ramos-Mejia, Veronica ;

Rouleau, Anne ;

Yang, Jiabi ;

Bosse, Marc ;

Lajoie, Gilles ;

Bhatia, Mickie .

NATURE, 2007, 448 (7157) :1015-U3

[2] Cytochrome oxidase activity in hippocampal synaptic mitochondria during aging: A quantitative cytochemical investigation [J].

Bertoni-Freddari, C ;

Fattoretti, P ;

Giorgetti, B ;

Solazzi, M ;

Balietti, M ;

Casoli, T ;

Di Stefano, G .

STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE: WHY GENUINE CONTROL OF AGING MAY BE FORESEEABLE, 2004, 1019 :33-36

[3] Carbon metabolism-mediated myogenic differentiation [J].

Bracha, Abigail L. ;

Ramanathan, Arvind ;

Huang, Sui ;

Ingber, Donald E. ;

Schreiber, Stuart L. .

NATURE CHEMICAL BIOLOGY, 2010, 6 (03) :202-204

[4] Derivation of pluripotent epiblast stem cells from mammalian embryos [J].

Brons, I. Gabrielle M. ;

Smithers, Lucy E. ;

Trotter, Matthew W. B. ;

Rugg-Gunn, Peter ;

Sun, Bowen ;

de Sousa Lopes, Susana M. Chuva ;

Howlett, Sarah K. ;

Clarkson, Amanda ;

Ahrlund-Richter, Lars ;

Pedersen, Roger A. ;

Vallier, Ludovic .

NATURE, 2007, 448 (7150) :191-U7

[5] The origin and efficient derivation of embryonic stem cells in the mouse [J].

Brook, FA ;

Gardner, RL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (11) :5709-5712

[6] Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo [J].

Camus, Anne ;

Perea-Gomez, Aitana ;

Moreau, Anne ;

Collignon, Jerome .

DEVELOPMENTAL BIOLOGY, 2006, 295 (02) :743-755

[7] EFFECTS OF OLIGOMYCIN ON RESPIRATION AND SWELLING OF ISOLATED LIVER MITOCHONDRIA [J].

CHAPPELL, JB ;

GREVILLE, GD .

NATURE, 1961, 190 (477) :502-&

[8] Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells [J].

Cho, Young Min ;

Kwon, Sujin ;

Pak, Youngmi Kim ;

Seol, Hye Won ;

Choi, Young Min ;

Park, Do Joon ;

Park, Kyong Soo ;

Lee, Hong Kyu .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 348 (04) :1472-1478

[9] Rates of behavior and aging specified by mitochondrial function during development [J].

Dillin, A ;

Hsu, AL ;

Arantes-Oliveira, NA ;

Lehrer-Graiwer, J ;

Hsin, H ;

Fraser, AG ;

Kamath, RS ;

Ahringer, J ;

Kenyon, C .

SCIENCE, 2002, 298 (5602) :2398-2401

[10] The Role of Hypoxia in Development of the Mammalian Embryo [J].

Dunwoodie, Sally L. .

DEVELOPMENTAL CELL, 2009, 17 (06) :755-773

← 1 2 3 4 5 6 →