文献类型：期刊文献

英文题名：MDH1-mediated malate-aspartate NADH shuttle maintains the activity levels of fetal liver hematopoietic stem cells

作者：Gu, Hao[1];Chen, Chiqi[1];Hao, Xiaoxin[1];Su, Ni[2];Huang, Dan[1];Zou, Yejun[2];Lin, Shu-Hai[3];Chen, Xianjun[2];Zheng, Denghao[1];Liu, Ligen[1];Yu, Zhuo[1];Xie, Li[1];Zhang, Yaping[1];He, Xiaoxiao[1];Lai, Xiaoyun[1];Zhang, Xiaocui[1];Chen, Guo-Qiang[1];Zhao, Yuzheng[2];Yang, Yi[2,4];Loscalzo, Joseph[5];Zheng, Junke[1,6]

机构：[1]Shanghai Jiao Tong Univ, Shanghai Tongren Hosp, Chinese Minist Educ,Sch Med, Hongqiao Int Inst Med,Key Lab Cell Differentiat &, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Chinese Acad Med Sci, Sch Pharm,Res Unit, State Key Lab Bioreactor Engn,Optogenet & Synthet, Shanghai, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Biol Sci, Ctr Excellence Brain Sci, Shanghai, Peoples R China;[5]Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA;[6]Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Reprod Med, Shanghai, Peoples R China

年份：2020

卷号：136

期号：5

起止页码：553

外文期刊名：BLOOD

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000560311900009)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (81825001, 81570093, 31971052, 31722033, 91649123, 31671484, and 91857202); National Basic Research Program of China (2019YFA0801800, 2018YFA0107000, 2019YFA0904800, and 2017YFA050400); Innovative Group of the National Natural Science Foundation of China (81721004; G.Q.-C.); Chinese Universities Scientific Fund; Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences (2019RU01, 2019-I2M-5-013); Major Program of the Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone (Stem Cell Strategic Biobank and Stem Cell Clinical Technology Transformation Platform; ZJ2018-ZD-004); Innovative Research Team of High-Level Local Universities in Shanghai, Natural Science Foundation of Shanghai (17ZR1415500); Shanghai Science and Technology Commission (19XD1422100 and 18JC1411900); Interdisciplinary Program of Shanghai Jiao Tong University (YG2016MS82); National Postdoctoral Program for Innovative Talents (BX201700157); US National Institutes of Health, National Heart, Lung, and Blood Institute (HL061795, Hl119145) (J.L.) and National Human Genome Research Institute (HG007690) (J.L.); and US National Institutes of Health, National Institute of General Medical Sciences (GM107618) (J.L.).

语种：英文

摘要：The connections between energy metabolism and stemness of hematopoietic stem cells (HSCs) at different developmental stages remain largely unknown. We generated a transgenic mouse line for the genetically encoded NADH/NAD+ sensor (SoNar) and dem-onstrate that there are 3 distinct fetal liver hematopoietic cell populations according to the ratios of SoNar fluorescence. SoNar-low cells had an enhanced level of mitochondrial res-piration but a glycolytic level similar to that of SoNar-high cells. Interestingly, 10% of SoNar-low cells were enriched for 65% of total immunophenotypic fetal liver HSCs (FL-HSCs) and contained approximately fivefold more functional HSCs than their SoNar-high counterparts. SoNar was able to monitor sensitively the dynamic changes of energy metabolism in HSCs both in vitro and in vivo. Mechanistically, STAT3 transactivated MDH1 to sustain the malate-aspartate NADH shuttle activity and HSC self-renewal and differentiation. We reveal an unexpected metabolic program of FL-HSCs and provide a powerful genetic tool for meta-bolic studies of HSCs or other types of stem cells.