Single-nucleus transcriptomics reveals a gatekeeper role for FoxP1 in primate cardiac aging  

作　　者：Yiyuan Zhang Yandong Zheng Si Wang Yanling Fan Yanxia Ye Yaobin Jing Zunpeng Liu Shanshan Yang Muzhao Xiong Kuan Yang Jinghao Hu Shanshan Che Qun Chu Moshi Song Guang-Hui Liu Weiqi Zhang Shuai Ma Jing Qu 

机构地区：[1]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 10o101,China [2]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [3]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [4]University of Chinese Academy of Sciences,Beijing100049,China [5]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [6]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China [7]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China [8]China National Center for Bioinformation,Beijing 100101,China [9]Aging Translational Medicine Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China [10]Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China [11]The Fifth People's Hospital of Chongqing,Chongqing 400062,China [12]Sino-Danish College,University of Chinese Academy of Sciences,Beijing 101408,China

出　　处：《Protein & Cell》2023年第4期279-293,共15页蛋白质与细胞（英文版）

基　　金：supported by the National Key Research and Development Program of China(2018YFC2000100);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000);the National Natural Science Foundation of China(81921006,92149301,92168201,82125011,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81901432,32000510,81861168034,32000500,81901433,81870228,81922027);the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401);the Program of the Beijing Natural Science Foundation(Z190019,JQ20031);K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08),Young Elite Scientists Sponsorship Program by CAST(YESS20200012,YESS20210002);The Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062);CAS Project for Young Scientists in Basic Research(YSBR-012),Youth Innovation Promotion Association of CAS(E1CAZW0401,2022083);the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14),the Tencent Foundation(2021-1045).

摘　　要：Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.

关 键 词：single-nucleus RNA-sequencing PRIMATE AGING FOxP1 CARDIOMYOCYTE 

分 类 号：R541[医药卫生—心血管疾病]