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Get Free AccessHematopoietic 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.
Javed K. Manesia, Zhuofei Xu, Dorien Broekaert, Ruben Boon, Alexander R. van Vliet, Guy Eelen, Thomas Vanwelden, Steve Stegen, Nick van Gastel, Alberto Pascual-Montano, Sarah‐Maria Fendt, Geert Carmeliet, Peter Carmeliet, Satish Khurana, Catherine M. Verfaillie (2015). Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways. , 15(3), DOI: https://doi.org/10.1016/j.scr.2015.11.001.
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Type
Article
Year
2015
Authors
15
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1016/j.scr.2015.11.001
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