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

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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Oburoglu L,Tardito S,Fritz V,de Barros SC,Merida P,Craveiro M,Mamede J,Cretenet G,Mongellaz C,An X,Klysz D,Touhami J,Boyer-Clavel M,Battini JL,Dardalhon V,Zimmermann VS,Mohandas N,Gottlieb E,Sitbon M,Kinet S,Taylo

doi

10.1016/j.stem.2014.06.002

subject

Has Abstract

pub_date

2014-08-07 00:00:00

pages

169-84

issue

2

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(14)00250-1

journal_volume

15

pub_type

杂志文章

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