Manesia Javed K, Xu Zhuofei, Broekaert Dorien, Boon Ruben, van Vliet Alex, Eelen Guy, Vanwelden Thomas, Stegen Steve, Van Gastel Nick, Pascual-Montano Alberto, Fendt Sarah-Maria, Carmeliet Geert, Carmeliet Peter, Khurana Satish, Verfaillie Catherine M
Inter-departmental Stem Cell Institute, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven, Belgium.
Laboratory of Cell Death Research and Therapy, KU Leuven, Leuven, Belgium.
Stem Cell Res. 2015 Nov;15(3):715-721. doi: 10.1016/j.scr.2015.11.001. Epub 2015 Nov 9.
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.
与成年骨髓（BM）不同，胎肝（FL）中的造血干细胞（HSC）会大量增殖，这对代谢有不同的需求。然而，目前尚未描述FL HSC中负责产生能量和细胞组成成分的代谢途径。在此，我们报告FL HSC比其BM对应物更多地使用依赖氧气的能量生成途径。对E14.5胎肝与BM来源的HSC进行RNA测序分析，发现参与氧化磷酸化（OxPhos）和柠檬酸循环（TCA）的基因表达水平增加。我们证明FL HSC比BM HSC含有更多的线粒体，这导致耗氧量和活性氧（ROS）生成水平增加。更高水平的DNA修复和抗氧化途径基因表达可能会预防ROS介导的（基因）毒性对FL HSC的影响。因此，我们首次强调了依赖氧气的途径在FL HSC中产生能量和细胞组成成分方面被低估的重要性。
