A single-cell atlas of immunocytes in the spleen of a mouse model of Wiskott-Aldrich syndrome

作者全名："Liang, Fangfang; Peng, Cheng; Luo, Xianze; Wang, Linlin; Huang, Yanyan; Yin, Le; Yue, Luming; Yang, Jun; Zhao, Xiaodong"

作者地址："[Liang, Fangfang; Luo, Xianze; Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Dept Rheumatism & Immunol, Chongqing, Peoples R China; [Liang, Fangfang; Wang, Linlin; Huang, Yanyan; Yin, Le; Yang, Jun] Shenzhen Childrens Hosp, Dept Rheumatism & Immunol, Shenzhen, Peoples R China; [Peng, Cheng] Third Peoples Hosp Shenzhen, Dept Radiol, Shenzhen, Peoples R China; [Yue, Luming] Singleron Biotechnol, Nanjing, Jiangsu, Peoples R China; [Zhao, Xiaodong] Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Childrens Hosp, Chongqing, Peoples R China; [Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Child Infect & Immun, Chongqing, Peoples R China"

通信作者："Zhao, XD (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Rheumatism & Immunol, Chongqing, Peoples R China.; Yang, J (通讯作者)，Shenzhen Childrens Hosp, Dept Rheumatism & Immunol, Shenzhen, Peoples R China."

来源：CELLULAR IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001111324000001

JCR分区：Q2

影响因子：3.7

年份：2023

卷号：393

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Wiskott-Aldrich syndrome; Single-cell RNA sequencing; Wiskott Aldrich syndrome protein; Spleen; WAS-KO mice

摘要："Wiskott-Aldrich syndrome (WAS) is a disorder characterized by rare X-linked genetic immune deficiency with mutations in the Was gene, which is specifically expressed in hematopoietic cells. The spleen plays a major role in hematopoiesis and red blood cell clearance. However, to date, comprehensive analyses of the spleen in wild-type (WT) and WASp-deficient (WAS-KO) mice, especially at the transcriptome level, have not been reported. In this study, single-cell RNA sequencing (scRNA-seq) was adopted to identify various types of immune cells and investigate the mechanisms underlying immune deficiency. We identified 30 clusters and 10 major cell subtypes among 11,269 cells; these cell types included B cells, T cells, dendritic cells (DCs), natural killer (NK) cells, monocytes, macrophages, granulocytes, stem cells and erythrocytes. Moreover, we evaluated gene expression differences among cell subtypes, identified differentially expressed genes (DEGs), and performed enrichment analyses to identify the reasons for the dysfunction in these different cell populations in WAS. Furthermore, some key genes were identified based on a comparison of the DEGs in each cell type involved in specific and nonspecific immune responses, and further analysis showed that these key genes were previously undiscovered pathology-related genes in WAS-KO mice. In summary, we present a landscape of immune cells in the spleen of WAS-KO mice based on detailed data obtained at single-cell resolution. These unprecedented data revealed the transcriptional characteristics of specific and nonspecific immune cells, and the key genes were identified, laying a foundation for future studies of WAS, especially studies into novel and underexplored mechanisms that may improve gene therapies for WAS."

基金机构：Shenzhen Science and Tech-nology Innovation Commission Funds [JCYJ20210324141011028]; Sanming Project of Medicine in Shenzhen [SZSM201812002]; National Key Research and Development Program of China [2021YFC2702000]; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties [SZGSP012]

基金资助正文："Funding This work was supported by grants from Shenzhen Science and Tech-nology Innovation Commission Funds (JCYJ20210324141011028) , Sanming Project of Medicine in Shenzhen (SZSM201812002) and National Key Research and Development Program of China (2021YFC2702000) , and Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (No. SZGSP012) ."