Glucose and Glutamine Metabolism Regulate Human Hematopoietic Stem Cell Lineage Specification

被引：209

作者：

Oburoglu, Leal ^{[1
,2
,3
]}

Tardito, Saverio ^{[4
]}

Fritz, Vanessa ^{[1
,2
,3
]}

de Barros, Stephanie C. ^{[1
,2
,3
]}

Merida, Peggy ^{[1
,2
,3
]}

Craveiro, Marco ^{[1
,2
,3
]}

Mamede, Joao ^{[1
,2
,3
]}

Cretenet, Gaspard ^{[1
,2
,3
]}

Mongellaz, Cedric ^{[1
,2
,3
]}

An, Xiuli ^{[5
,6
]}

Klysz, Dorota ^{[1
,2
,3
]}

Touhami, Jawida ^{[1
,2
,3
]}

Boyer-Clavel, Myriam ^{[1
,2
]}

Battini, Jean-Luc ^{[1
,2
,3
]}

Dardalhon, Valerie ^{[1
,2
,3
]}

Zimmermann, Valerie S. ^{[1
,2
,3
]}

Mohandas, Narla ^{[5
]}

Gottlieb, Eyal ^{[4
]}

Sitbon, Marc ^{[1
,2
,3
]}

Kinet, Sandrina ^{[1
,2
,3
]}

Taylor, Naomi ^{[1
,2
,3
]}

机构：

[1] Univ Montpellier I, CNRS, Inst Genet Mol Montpellier, UMR5535, F-34293 Montpellier, France

[2] Univ Montpellier 2, CNRS, Inst Genet Mol Montpellier, UMR5535, F-34293 Montpellier, France

[3] Lab Excellence GR Ex, F-75015 Paris, France

[4] Beatson Inst, Canc Res UK, Glasgow G61 1BD, Lanark, Scotland

[5] New York Blood Ctr, New York, NY 10032 USA

[6] Zhengzhou Univ, Dept Bioengn, Zhengzhou 450051, Peoples R China

来源：

CELL STEM CELL | 2014年 / 15卷 / 02期

关键词：

DISTINCT STAGES; TCA CYCLE; ACID; DIFFERENTIATION; TRANSPORT; PATHWAY; CANCER; GLYCOLYSIS; EXPRESSION; GROWTH;

D O I：

10.1016/j.stem.2014.06.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The metabolic state of quiescent hematopoietic stem cells (HSCs) is an important regulator of self-renewal, but it is unclear whether or how metabolic parameters contribute to HSC lineage specification and commitment. Here, we show that the commitment of human and murine HSCs to the erythroid lineage is dependent upon glutamine metabolism. HSCs require the ASCT2 glutamine transporter and active glutamine metabolism for erythroid specification. Blocking this pathway diverts EPO-stimulated HSCs to differentiate into myelomonocytic fates, altering in vivo HSC responses and erythroid commitment under stress conditions such as hemolytic anemia. Mechanistically, erythroid specification of HSCs requires glutamine-dependent de novo nucleotide biosynthesis. Exogenous nucleosides rescue erythroid commitment of human HSCs under conditions of limited glutamine catabolism, and glucose-stimulated nucleotide biosynthesis further enhances erythroid specification. Thus, the availability of glutamine and glucose to provide fuel for nucleotide biosynthesis regulates HSC lineage commitment under conditions of metabolic stress.

引用

页码：169 / 184

页数：16

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