title: Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways.
abstract: 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.
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium.
authors.forename: Javed K
authors.initials: JK
authors.lastname: Manesia
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium.
authors.forename: Zhuofei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium.
authors.forename: Dorien
authors.initials: D
authors.lastname: Broekaert
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Boon
authors.affiliation: Laboratory of Cell Death Research and Therapy, KU Leuven, Leuven, Belgium.
authors.forename: Alex
authors.initials: A
authors.lastname: van Vliet
authors.affiliation: Laboratory of Angiogenesis and Neurovascular Link, KU Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Eelen
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanwelden
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Stegen
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Nick
authors.initials: N
authors.lastname: Van Gastel
authors.affiliation: Functional Bioinformatics Group, National Center for Biotechnology-CSIC, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual-Montano
authors.affiliation: Laboratory of Cellular Metabolism and Metabolic Regulation, KU Leuven, Leuven, Belgium.
authors.forename: Sarah-Maria
authors.initials: SM
authors.lastname: Fendt
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.affiliation: Laboratory of Angiogenesis and Neurovascular Link, KU Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium. Electronic address: svkanand@gmail.com.
authors.forename: Satish
authors.initials: S
authors.lastname: Khurana
authors.affiliation: Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium. Electronic address: Catherine.verfaillie@med.kuleuven.be.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
mesh_terms: D002478:Cells, Cultured; D005333:Fetus; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000276:immunology*; D053858:Metabolic Networks and Pathways; D010085:Oxidative Phosphorylation
keywords: Bone marrow; Fetal liver; Hematopoietic stem cells; Metabolism; Oxidative phosphorylation; Self-renewal