Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis  

作　　者：Jiaqi Qiang Shan Yu Jun Li Yu Rong Xiaoshuang Wang Yong Zhu Fang Wang 

机构地区：[1]State Key Laboratory of Medical Molecular Biology,Department of Biochemistry and Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China [2]The Key Laboratory of RNA and Hematopoietic Regulation,Chinese Academy of Medical Sciences,Beijing 100005,China [3]Eight-Year Medical Doctor Program,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [4]Department of Endocrinology,Key Laboratory of Endocrinology of National Health Commission,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China [5]Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province,Hangzhou 310030,China [6]Department of Cardiovascular Medicine,Chongqing Emergency Medical Center,Chongqing University Central Hospital,Chongqing 400014,China [7]College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China

出　　处：《Journal of Molecular Cell Biology》2024年第7期30-45,共16页分子细胞生物学报(英文版)

基　　金：supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-040 to F.W.);the National Key Research and Development Program of China(2021YFA1102400 to F.W.,2019YFA0111700 to X.W.);the National Natural Science Foundation of China(82022001 and 81970103 to F.W.,82070111 to Y.Z.).

摘　　要：Alternative polyadenylation(APA)is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites(PASs).APA is involved in lymphocyte activation;however,its role throughout the entire differentiation trajectory remains elusive.Here,we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells(HSPCs)to terminally differentiated lymphocytes.This analysis covered 19973 cells of 12 clusters from five lineages(B cells,CD4^(+)T cells,CD8^(+)T cells,natural killer cells,and plasmacytoid dendritic cells).A total of 2364 genes exhibited differential 3'-untranslated region(3'UTR)PAS usage,and 3021 genes displayed differential intronic cleavage during lymphoid differentiation.We observed a global trend of 3'UTR shortening during lymphoid differentiation.Nevertheless,specific events of both 3'UTR shortening and lengthening were also identified within each cluster.The APA patterns delineated three differentiation stages:HSPCs,precursor cells,and mature cells.Moreover,we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes(TCF7 and NFATC2IP),immune function-related genes(BCL2,CD5,CD28,GOLT1B,and TMEM59),and protein ubiquitination-related genes(UBE2G1,YPEL5,and SUMO3).These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.

关 键 词：alternative polyadenylation HEMATOPOIESIS lymphoid differentiation post-transcription SINGLE-CELL 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]