中国病理生理杂志2024，Vol.40Issue(5)：769-776,8.DOI:10.3969/j.issn.1000-4718.2024.00.015
胚胎造血干细胞发育全程线粒体动态特征及功能研究
Dynamic changes and function of mitochondria in development of em-bryonic hematopoietic stem cells
摘要
Abstract
AIM:To describe the dynamic characteristics of mitochondria in the development of mouse embryonic hematopoietic stem cells,and to explore the function of mitochondria in this process.METHODS:Single-cell transcrip-tomic data of continuous developmental hematopoietic stem cell-related populations were analyzed to describe the dynamic changes of genes related to mitochondrial synthesis and energy metabolism.To explore the dynamic changes in the number and activity of mitochondria during the development of hematopoietic stem cells,we detected the mitochondrial number and mitochondrial membrane potential of the cells in each stage of hematopoietic stem cell development by fluorescent probe staining combined with flow cytometry.We added small molecule inhibitors of mitochondrial synthesis and energy metabolism and used hematopoietic cell colony formation assay to detect the effect of mitochondrial function inhibition on the induction of hematopoietic products in vitro.RESULTS:(1)Single-cell transcriptome analysis showed that genes in-volved in mitochondrial synthesis and oxidative phosphorylation were significantly up-regulated in endothelial cell and type Ⅰ pre-hematopoietic stem cell compared with those involved in glycolysis,and these genes could significantly distinguish continuous dynamic populations.(2)The results of fluorescence staining and flow cytometry analysis showed that mito-chondrial number and mitochondrial membrane potential had an increasing trend during the continuous development of he-matopoietic stem cell,reaching the highest level in the precursor stage of type 2 pre-hematopoietic stem cell,and decreasing in the mature hematopoietic stem cell of fetal liver.(3)Compared with control group,inhibition of mitochondrial respirato-ry chain Ⅰ and Ⅴ significantly reduced the number of hematopoietic colonies(P<0.05).CONCLUSION:(1)Genes re-lated to mitochondrial synthesis and oxidative phosphorylation are highly expressed in hemogenic endothelial cells and type Ⅰpre-hematopoietic stem cells,and can be used to distinguish continuous developing populations.(2)The mitochondrial number and mitochondrial membrane potential increased continuously during hematopoietic stem cell development and reached the highest level in type 2 pre-hematopoietic stem cells.(3)Inhibition of mitochondrial respiratory chain Ⅰ and Ⅴ significantly reduced the production of hematopoietic products in vitro.关键词
造血干细胞/线粒体/氧化磷酸化/生血内皮细胞Key words
hematopoietic stem cells/mitochondria/oxidative phosphorylation/hemogenic endothelial cells分类
医药卫生引用本文复制引用
张容,赵海鑫,周杰,柳迪,兰雨,刘兵..胚胎造血干细胞发育全程线粒体动态特征及功能研究[J].中国病理生理杂志,2024,40(5):769-776,8.基金项目
国家自然科学基金资助项目(No.82000107 （）
No.82070104) （）
国家重点研发计划(No.2020YFA0113300) （No.2020YFA0113300）
