The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche

Cell Stem Cell. 2010 Sep 3;7(3):380-90. doi: 10.1016/j.stem.2010.07.011.

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-1alpha are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1alpha. These findings reveal an important transcriptional network that regulates HSC metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Energy Metabolism
  • Glycolysis*
  • Hematopoietic Stem Cells / metabolism*
  • Homeodomain Proteins
  • Hypoxia*
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Stem Cell Niche / metabolism*
  • Transcriptional Activation

Substances

  • Hif1a protein, mouse
  • Homeodomain Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Meis1 protein, mouse
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins