A novel reporter mouse line for studying alveolar macrophages  

作　　者：Xiaoyun Zhao Liang Li Hongxiang Sun Xiaoli Jiang Wenjuan Bai Ningbo Wu Jing Wang Bing Su 

机构地区：[1]Shanghai Institute of Immunology,Department of Immunology and Microbiology,and the Ministry of Education Key Laboratory of Cell Death and Differentiation,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Center for Immune-Related Diseases at Shanghai Institute of Immunology,Department of Gastroenterology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [3]Shanghai Jiao Tong University School of Medicine—Yale Institute for Immune Metabolism,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [4]Key Laboratory of Molecular Radiation Oncology of Hunan Province,Xiangya Hospital,Central South University,Changsha 410008,China

出　　处：《Science China(Life Sciences)》2023年第11期2527-2542,共16页中国科学（生命科学英文版）

基　　金：supported in part by the National Key Research and Development Program of China(2021YFA1301400);the National Natural Science Foundation of China(31930035,91942311,32061143028,32170895,82100575);China Postdoctoral Science Foundation(2021M692127,2022T150423);Shanghai Science and Technology Commission(20410714000,20JC1410100,22JC1402600,22ZR1480700,22QA1408000);Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases.

摘　　要：Alveolar macrophages(AMs)are self-maintained immune cells that play vital roles in lung homeostasis and immunity.Although reporter mice and culture systems have been established for studying macrophages,an accurate and specific reporter line for alveolar macrophage study is still not available.Here we reported a novel Rspo1-tdTomato gene reporter mouse line that could specifically label mouse AMs in a cell-intrinsic manner.Using this reporter system,we visualized the dynamics of alveolar macrophages intravitally under steady state and characterized the alveolar macrophage differentiation under in vitro condition.By performing ATAC-seq,we found that insertion of the tdTomato cassette in the Rspo1 locus increased the accessibility of a PPARE motif within the Rspo1 locus and revealed a potential regulation by key transcription factor PPAR-γfor alveolar macrophage differentiation in vitro and in vivo.Consistently,perturbation of PPAR-γby its agonist rosiglitazone or inhibitor GW9662 resulted in corresponding alteration of tdTomato expression in alveolar macrophages together with the transcription of PPAR-γdownstream target genes.Furthermore,global transcriptomic analyses of AMs from the wild type mice and the Rspo1-tdTomato mice showed comparable gene expression profiles,especially those AM-specific genes,confirming that the insertion of the tdTomato cassette in the Rspo1 locus does not impact the cell identity and biological function of AMs under normal condition.Taken together,our study provides an alternative tool for in vivo and in vitro labeling of alveolar macrophages with high specificity which could also be utilized as an indicator of PPAR-γactivity for future development of PPAR-γspecific targeting drugs.

关 键 词：alveolar macrophage gene reporter mice PPAR-Γ R-spondin 1 ATAC-seq 

分 类 号：R392[医药卫生—免疫学]