期刊
CELL AND BIOSCIENCE
卷 5, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13578-015-0020-3
关键词
Stem cells; Metabolism; Hypoxia; Hypoxic regulation of metabolism; Human hematopoietic progenitor and stem cells; HPSCs
资金
- American Heart Association (AHA)
- Gilead Research Scholars Program in Cardiovascular Disease
- NIH [1R01CA172268]
- CPRIT [RP140402]
- March of Dimes Foundation Award [1-FY14-201]
- National Natural Science Foundation of China [81370654, 81471524, 31171409]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning and the Pujiang Program [13PJ1405600]
- Scientific and Technological Research Council of Turkey (TUBITAK)
- Marie Curie Action COFUND of the 7th. Framework Programme (FP7) of the European Commission [115C039]
- Science Academy of Turkey Young Scientist Award Program
- Yeditepe University, Istanbul, Turkey
Background: Adult hematopoietic stem cells (HSCs) are maintained in a microenvironment, known as niche in the endosteal regions of the bone marrow. This stem cell niche with low oxygen tension requires HSCs to adopt a unique metabolic profile. We have recently demonstrated that mouse long-term hematopoietic stem cells (LT-HSCs) utilize glycolysis instead of mitochondrial oxidative phosphorylation as their main energy source. However, the metabolic phenotype of human hematopoietic progenitor and stem cells (HPSCs) remains unknown. Results: We show that HPSCs have a similar metabolic phenotype, as shown by high rates of glycolysis, and low rates of oxygen consumption. Fractionation of human mobilized peripheral blood cells based on their metabolic footprint shows that cells with a low mitochondrial potential are highly enriched for HPSCs. Remarkably, low MP cells had much better repopulation ability as compared to high MP cells. Moreover, similar to their murine counterparts, we show that Hif-1 alpha is upregulated in human HPSCs, where it is transcriptionally regulated by Meis1. Finally, we show that Meis1 and its cofactors Pbx1 and HoxA9 play an important role in transcriptional activation of Hif-1 alpha in a cooperative manner. Conclusions: These findings highlight the unique metabolic properties of human HPSCs and the transcriptional network that regulates their metabolic phenotype.
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