Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification

Leal Oburoglu, Saverio Tardito, Vanessa Fritz, Stéphanie C. De Barros, Peggy Merida, Marco Craveiro, Joao Filipe Inacio Mamede, Gaspard Cretenet, Cédric Mongellaz, Xiuli An, Dorota Klysz, Jawida Touhami, Myriam Boyer-Clavel, Jean Luc Battini, Valérie Dardalhon, Valérie S. Zimmermann, Narla Mohandas, Eyal Gottlieb, Marc Sitbon, Sandrina Kinet*Naomi Taylor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)169-184
Number of pages16
JournalCell stem cell
Volume15
Issue number2
DOIs
StatePublished - Aug 7 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification'. Together they form a unique fingerprint.

Cite this