Journal
CELL STEM CELL
Volume 7, Issue 3, Pages 380-390Publisher
CELL PRESS
DOI: 10.1016/j.stem.2010.07.011
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Funding
- American Heart Association
- Donald W. Reynolds Center for Clinical Cardiovascular Research
- Welch Foundation [I-1701]
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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-1 alpha are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1 alpha. These findings reveal an important transcriptional network that regulates HSC metabolism.
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