PMID- 26599326
OWN - NLM
STAT- MEDLINE
DCOM- 20161109
LR  - 20170920
IS  - 1876-7753 (Electronic)
IS  - 1873-5061 (Linking)
VI  - 15
IP  - 3
DP  - 2015 Nov
TI  - Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by 
      oxidative metabolic pathways.
PG  - 715-721
LID - S1873-5061(15)00154-3 [pii]
LID - 10.1016/j.scr.2015.11.001 [doi]
AB  - 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.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Manesia, Javed K
AU  - Manesia JK
AD  - Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of 
      Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 
      Leuven, Belgium.
FAU - Xu, Zhuofei
AU  - Xu Z
AD  - Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of 
      Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 
      Leuven, Belgium.
FAU - Broekaert, Dorien
AU  - Broekaert D
AD  - Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of 
      Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 
      Leuven, Belgium.
FAU - Boon, Ruben
AU  - Boon R
AD  - Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of 
      Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 
      Leuven, Belgium.
FAU - van Vliet, Alex
AU  - van Vliet A
AD  - Laboratory of Cell Death Research and Therapy, KU Leuven, Leuven, Belgium.
FAU - Eelen, Guy
AU  - Eelen G
AD  - Laboratory of Angiogenesis and Neurovascular Link, KU Leuven, Leuven, Belgium; 
      Laboratory of Angiogenesis and Neurovascular Link, Leuven, Belgium.
FAU - Vanwelden, Thomas
AU  - Vanwelden T
AD  - Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of 
      Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 
      Leuven, Belgium.
FAU - Stegen, Steve
AU  - Stegen S
AD  - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
FAU - Van Gastel, Nick
AU  - Van Gastel N
AD  - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
FAU - Pascual-Montano, Alberto
AU  - Pascual-Montano A
AD  - Functional Bioinformatics Group, National Center for Biotechnology-CSIC, Madrid, 
      Spain.
FAU - Fendt, Sarah-Maria
AU  - Fendt SM
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, KU Leuven, Leuven, 
      Belgium.
FAU - Carmeliet, Geert
AU  - Carmeliet G
AD  - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
FAU - Carmeliet, Peter
AU  - Carmeliet P
AD  - Laboratory of Angiogenesis and Neurovascular Link, KU Leuven, Leuven, Belgium; 
      Laboratory of Angiogenesis and Neurovascular Link, Leuven, Belgium.
FAU - Khurana, Satish
AU  - Khurana S
AD  - 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.
FAU - Verfaillie, Catherine M
AU  - Verfaillie CM
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151109
PL  - England
TA  - Stem Cell Res
JT  - Stem cell research
JID - 101316957
SB  - IM
MH  - Cells, Cultured
MH  - Fetus
MH  - Hematopoietic Stem Cells/cytology/*metabolism
MH  - Humans
MH  - Liver/cytology/*immunology
MH  - Metabolic Networks and Pathways
MH  - Oxidative Phosphorylation
OTO - NOTNLM
OT  - Bone marrow
OT  - Fetal liver
OT  - Hematopoietic stem cells
OT  - Metabolism
OT  - Oxidative phosphorylation
OT  - Self-renewal
EDAT- 2015/11/26 06:00
MHDA- 2016/11/10 06:00
CRDT- 2015/11/25 06:00
PHST- 2015/07/10 00:00 [received]
PHST- 2015/10/16 00:00 [revised]
PHST- 2015/11/02 00:00 [accepted]
PHST- 2015/11/25 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/11/10 06:00 [medline]
AID - S1873-5061(15)00154-3 [pii]
AID - 10.1016/j.scr.2015.11.001 [doi]
PST - ppublish
SO  - Stem Cell Res. 2015 Nov;15(3):715-721. doi: 10.1016/j.scr.2015.11.001. Epub 2015 
      Nov 9.