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BMAL1 modulates glutamine supply to control hematopoietic stem and progenitor cell expansion - PubMed

5 hours ago
  • #Glutamine Metabolism
  • #Circadian Clock
  • #Hematopoiesis
  • BMAL1, a core circadian clock component, is expressed in zebrafish CHT endothelial cells (ECs) and non-cell autonomously affects hematopoietic stem and progenitor cells (HSPCs).
  • Endothelial-specific dominant-negative Bmal1a zebrafish lines show increased HSPC numbers due to enhanced proliferation.
  • RNA-sequencing reveals downregulation of glud1a in dominant-negative bmal1a ECs, leading to elevated glutamine levels in the CHT.
  • The bmal1a-glud1a-glutamine pathway is identified as a regulator of HSPC expansion.
  • This glutamine synthesis pathway is conserved in the mouse fetal liver niche, with hepatocytes as the likely glutamine source.
  • EC BMAL1 controls bioavailable glutamine for HSPCs by regulating glutamine synthesis genes.