Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification

Oburoglu, L. et al. (2014) Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell, 15(2), pp. 169-184. (doi: 10.1016/j.stem.2014.06.002) (PMID:24953180)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tardito, Dr Saverio
Authors: Oburoglu, L., Tardito, S., Fritz, V., de Barros, S. C., Merida, P., Craveiro, M., Mamede, J., Cretenet, G., Mongellaz, C., An, X., Klysz, D., Touhami, J., Boyer-Clavel, M., Battini, J.-L., Dardalhon, V., Zimmermann, V. S., Mohandas, N., Gottlieb, E., Sitbon, M., Kinet, S., and Taylor, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Stem Cell
Publisher:Elsevier
ISSN:1934-5909
ISSN (Online):1875-9777

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