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

      Cell Stem Cell

      Transcriptional Activation, metabolism, Stem Cell Niche, Neoplasm Proteins, Mice, Inbred C57BL, Mice, Metabolomics, Hypoxia-Inducible Factor 1, alpha Subunit, Homeodomain Proteins, Hematopoietic Stem Cells, Glycolysis, Energy Metabolism, Anoxia, Animals

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          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. Copyright 2010 Elsevier Inc. All rights reserved.

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          Author and article information

          Journal
          10.1016/j.stem.2010.07.011
          4159713
          20804973

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