title: Hypoxic metabolism in human hematopoietic stem cells.
abstract: 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-1α 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-1α in a cooperative manner.
  
  
  CONCLUSIONS
  These findings highlight the unique metabolic properties of human HPSCs and the transcriptional network that regulates their metabolic phenotype.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.|Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, 34755 Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Kocabas
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Chongqing South Road 280, Shanghai, 200025 China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Bingzhou Medical University, Taishan Scholar Program, Yantai, 264003 China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Chongqing South Road 280, Shanghai, 200025 China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Departments of Pediatrics and Genetics, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.affiliation: Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kimura
authors.affiliation: Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.
authors.forename: SuWannee
authors.initials: S
authors.lastname: Thet
authors.affiliation: Department of Clinical Pathology, El Galaa Hospital, Cairo, Egypt.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Elshamy
authors.affiliation: Faculty of Medicine Ain Shams University, El Abbaseya, Cairo, Egypt.
authors.forename: Hesham
authors.initials: H
authors.lastname: Abouellail
authors.affiliation: Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Muralidhar
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Chongqing South Road 280, Shanghai, 200025 China.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Liu
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China.
authors.forename: Chiqi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 USA.
authors.forename: Hesham A
authors.initials: HA
authors.lastname: Sadek
authors.affiliation: Departments of Physiology and Developmental Biology, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Chongqing South Road 280, Shanghai, 200025 China.
authors.forename: Junke
authors.initials: J
authors.lastname: Zheng
keywords: HPSCs; Human hematopoietic progenitor and stem cells; Hypoxia; Hypoxic regulation of metabolism; Metabolism; Stem cells