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Cell Stem Cell. 2014 Aug 7;15(2):169-84. doi: 10.1016/j.stem.2014.06.002. Epub 2014 Jun 19.

Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification.

Author information

1
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Universités de Montpellier 1 et 2, F-34293 Montpellier, France; Laboratory of Excellence GR-Ex, Paris 75015, France.
2
Cancer Research UK, Beatson Institute, Glasgow, G61 1BD, UK.
3
New York Blood Center, New York, NY 10032, USA; Department of Bioengineering, Zhengzhou University, Zhengzhou 450051, China.
4
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Universités de Montpellier 1 et 2, F-34293 Montpellier, France.
5
New York Blood Center, New York, NY 10032, USA.
6
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Universités de Montpellier 1 et 2, F-34293 Montpellier, France; Laboratory of Excellence GR-Ex, Paris 75015, France. Electronic address: kinet@igmm.cnrs.fr.
7
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Universités de Montpellier 1 et 2, F-34293 Montpellier, France; Laboratory of Excellence GR-Ex, Paris 75015, France. Electronic address: taylor@igmm.cnrs.fr.

Erratum in

  • Cell Stem Cell. 2014 Nov 6;15(5):666-8.

Abstract

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.

PMID:
24953180
DOI:
10.1016/j.stem.2014.06.002
[Indexed for MEDLINE]
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