Alterations in immune cell heterogeneities in the brain of aged zebrafish using single-cell resolution  

作　　者：Jiangyong He Fangying Zhao Bingyue Chen Nianfei Cui Zhifan Li Jie Qin Lingfei Luo Congjian Zhao Li Li 

机构地区：[1]Institute of Developmental Biology and Regenerative Medicine,Key Laboratory of Freshwater Fish Reproduction and Development,Ministry of Education,Southwest University,Chongqing,400715,China [2]Research Center of Stem cells and Aging,Chongqing Institute of Green and Intelligent Technology,Chinese Academy of Sciences,Chongqing,400714,China [3]Chongqing Engineering Research Center of Medical Electronics and Information Technology,School of Bioinformatics,Chongqing University of Posts and Telecommunications,Chongqing,400065,China

出　　处：《Science China(Life Sciences)》2023年第6期1358-1378,共21页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Project (2019YFA802703);the National Natural Science Foundation of China (32270873,32000568,31822033);the Natural Science Foundation of Chongqing (CSTC2020JCYJ-MSXMX0104);Fundamental Research Funds for the Central Universities Grant (XDJK2020C041)。

摘　　要：Immunocytes,including the microglia,are crucial in the neurodegenerative process in old people.However,the understanding regarding microglia heterogeneity and other involved immunocytes remains elusive.We analyzed 26,456 immunocytes from 12-and 26-month-old zebrafish brains at single-cell resolution.Microglia and T lymphocytes were detected in the brain at both time points.Two types of microglia were annotated,namely,ac+microglia and xr+microglia,which were clustered into subsets 1,2,3,4,5,and subsets 6,7,8,9,respectively.Diversified microglia predominated the adult brains and cooperated with T cells to perform the functions of immune response and neuronal nutrition.We validated the specific microglia markers.The novel transgenic lines,Tg(lgals3bpb:e GFP)and Tg(apoc1:e GFP),were created,which faithfully labeled ac+microglia and served as valuable labeling tools.However,the microglia population reduced while T cells of six subtypes intriguingly increased to serve as the primary immune cells in aged brains.Unlike in 12-month-old brains,T cells,together with microglia,exhibited a coordinated signature of inflammation in the 26-month-old brains.Our findings revealed the immunocytes atlas in aged zebrafish brains.It implied the involvement of microglia and T cells in the progression of neurodegeneration in aging.

关 键 词：aging scRNA-seq MICROGLIA T lymphocyte INFLAMMATION ZEBRAFISH 

分 类 号：R392[医药卫生—免疫学]