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.
- SourceAvailable from: Thimios A MitsiadisFrontiers in Physiology 03/2015; 6. DOI:10.3389/fphys.2015.00099 · 3.50 Impact Factor
- Frontiers in Physiology 03/2015; 5. · 3.50 Impact Factor
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ABSTRACT: Living organisms require a constant supply of safe and efficient energy to maintain homeostasis and to allow locomotion of single cells, tissues and the entire organism. The source of energy can be glycolysis, a simple series of enzymatic reactions in the cytosol, or a much more complex process in the mitochondria, oxidative phosphorylation (OXPHOS). In this review we will examine how does the organism balance its source of energy in two seemingly distinct and unrelated processes: haematopoiesis and exercise. In both processes we will show the importance of the metabolic program and its regulation. We will also discuss the importance of oxygen availability in the context of the nutrient and cellular state, and address the emerging role of lactate as an energy source and signaling molecule in health and disease.Mitochondrion 09/2014; 19. DOI:10.1016/j.mito.2014.09.007 · 3.52 Impact Factor