The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche

Tugba Simsek, Fatih Kocabas, Junke Zheng, Ralph J DeBerardinis, Ahmed I. Mahmoud, Eric N Olson, Jay W Schneider, Chengcheng Zhang, Hesham A Sadek

Research output: Contribution to journalArticle

560 Scopus citations

Abstract

Bone marrow transplantation is the primary therapy for numerous hematopoietic disorders. The efficiency of bone marrow transplantation depends on the function of long-term hematopoietic stem cells (LT-HSCs), which is markedly influenced by their hypoxic niche. Survival in this low-oxygen microenvironment requires significant metabolic adaptation. Here, we show that LT-HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands. We used flow cytometry to identify a unique low mitochondrial activity/glycolysis-dependent subpopulation that houses the majority of hematopoietic progenitors and LT-HSCs. Finally, we demonstrate that Meis1 and Hif-1α are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1α. These findings reveal an important transcriptional network that regulates HSC metabolism.

Original languageEnglish (US)
Pages (from-to)380-390
Number of pages11
JournalCell Stem Cell
Volume7
Issue number3
DOIs
StatePublished - Sep 3 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche'. Together they form a unique fingerprint.

  • Cite this