Authors:
Tugba Simsek, Fatih Kocabas, Junke Zheng, Ralph J. DeBerardinis, Ahmed I. Mahmoud, Eric N. Olson, Jay W. Schneider, Cheng Cheng Zhang, & Hesham A. Sadek
Summary:
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.
Source:
Cell Stem Cell; Vol. 7, Issue 3, 380-390 (09/03/10)