Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny  

作　　者：Yazhou Cuiand Guangjin Pan Fei Li Yanling Zhu Tianyu Wang Jun Tang Yuhua Huang Jiaming Gu Yuchan Mai Mingquan Wang Zhishuai Zhang Jiaying Ning Baoqiang Kang Junwei Wang Tiancheng Zhou Yazhou Cui Guangjin Pan 

机构地区：[1]Key Laboratory of Immune Response and Immunotherapy,Joint School of Life Sciences,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou Medical University,Guangzhou 510530,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]Centre for Regenerative Medicine and Health,Hong Kong Institute of Science and Innovation,Chinese Academy of Sciences,Hong Kong,China [4]Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangdong‑Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine,Center for Cell Lineage and Cell Therapy,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [5]GIBH‑HKU Guangdong‑Hong Kong Stem Cell and Regenerative Medicine Research Centre,GIBH‑CUHK Joint Research Laboratory On Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [6]South China Institute for Stem Cell Biology and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [7]Key Lab for Rare&Uncommon Diseases of Shandong Province,Biomedical Sciences College&Shandong Medicinal Biotechnology Centre,Shandong First Medical University&Shandong Academy of Medical Sciences,Ji’nan 250117,Shandong,China

出　　处：《Cell Regeneration》2024年第1期287-304,共18页细胞再生(英文)

基　　金：National Key Research and Development Program of China,Stem Cell and Translational Research(2022YFA1105001);Research Funds from Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong SAR,P.R.China;National Natural Science Foundation of China(31971374,32171451);Science and Technology Planning Project of Guangdong Province,China(2023B1212060050,2023B1212120009);Youth Innovation Promotion Association of the Chinese Academy of Sciences(to Y.Z.2023373);China Postdoctoral Science Foundation Funded Project(2023M733516);Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation(ZXXM202201);Guangzhou Key Research and Development Program(202206010041);Guangzhou Science and Technology Program General project(2024A04J3801);Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine(2020B1212060052);Guangdong Province Special Program for Outstanding Talents(to G.P.,2019JC05Y463).

摘　　要：Human hematopoiesis starts at early yolk sac and undergoes site-and stage-specific changes over development.The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood.Here,we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells(HSPCs)at different developmental stages,including yolk-sac(YS),AGM,fetal liver(FL),umbilical cord blood(UCB)and adult peripheral blood(PB)mobilized HSPCs.These stage-specific HSPCs display differential intrinsic properties,such as metabolism,self-renewal,differentiating potentialities etc.We then generated highly co-related gene regulatory network(GRNs)modules underlying the differential HSC key properties.Particularly,we identified GRNs and key regulators control-ling lymphoid potentiality,self-renewal as well as aerobic respiration in human HSCs.Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells.Therefore,GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

关 键 词：Hematopoietic stem cell Transcription factors Lineage potential Gene regulatory networks Human induced pluripotent stem cells Hematopoietic differentiation 

分 类 号：R57[医药卫生—消化系统]