The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche.
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.
Simsek
Tugba
T
Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Kocabas
Fatih
F
Zheng
Junke
J
Deberardinis
Ralph J
RJ
Mahmoud
Ahmed I
AI
Olson
Eric N
EN
Schneider
Jay W
JW
Zhang
Cheng Cheng
CC
Sadek
Hesham A
HA
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
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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