Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways

Stem Cell Research

卷:15

Steve Stegen¹  Nick Van Gastel¹  Geert Carmeliet¹  Alberto Pascual-Montano²  Dorien Broekaert³  Catherine M. Verfaillie³  Thomas Vanwelden³  Javed K. Manesia³  Satish Khurana³  Ruben Boon³  Zhuofei Xu³  Guy Eelen⁴  Peter Carmeliet⁴  Alex van Vliet⁵  Sarah-Maria Fendt⁶ 

[1] Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium;

[2] Functional Bioinformatics Group, National Center for Biotechnology-CSIC, Madrid, Spain;

[3] Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium;

[4] Laboratory of Angiogenesis and Neurovascular Link, KU Leuven, Leuven, Belgium;

[5] Laboratory of Cell Death Research and Therapy, KU Leuven, Leuven, Belgium;

[6] Laboratory of Cellular Metabolism and Metabolic Regulation, KU Leuven, Leuven, Belgium;

关键词: Hematopoietic stem cells;    Fetal liver;    Bone marrow;    Metabolism;    Oxidative phosphorylation;    Self-renewal;   

DOI  :  10.1016/j.scr.2015.11.001

来源: DOAJ

【 摘 要 】

Hematopoietic stem cells (HSCs) in the fetal liver (FL) unlike adult bone marrow (BM) proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos) and the citric acid cycle (TCA). We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS) production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (geno)toxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

【 授权许可】

Unknown