title: The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche.
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.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Tugba
authors.initials: T
authors.lastname: Simsek
authors.forename: Fatih
authors.initials: F
authors.lastname: Kocabas
authors.forename: Junke
authors.initials: J
authors.lastname: Zheng
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Deberardinis
authors.forename: Ahmed I
authors.initials: AI
authors.lastname: Mahmoud
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Jay W
authors.initials: JW
authors.lastname: Schneider
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
authors.forename: Hesham A
authors.initials: HA
authors.lastname: Sadek
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006019:Glycolysis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D055153:Stem Cell Niche / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C497443:Hif1a protein, mouse; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins
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