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-1α are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1α. These findings reveal an important transcriptional network that regulates HSC metabolism.
Original language | English (US) |
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Pages (from-to) | 380-390 |
Number of pages | 11 |
Journal | Cell Stem Cell |
Volume | 7 |
Issue number | 3 |
DOIs | |
State | Published - Sep 3 2010 |
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Cell Biology