scRNA-seq profiling of neonatal and adult thymus-derived CD4+ T cells by a T cell origin-time tracing model
作者机构：Shanghai Institute of ImmunologyDepartment of Immunology and Microbiologyand the Ministry of Education Key Laboratory of Cell Death and DifferentiationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Tumor BiologyShanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Center for Human Translational Immunology at Shanghai Institute of ImmunologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Jiao Tong University School of Medicine–Yale Institute for Immune MetabolismShanghai Jiao Tong University School of MedicineShanghai 200025China Key Laboratory of Molecular Radiation Oncology of Hunan ProvinceXiangya HospitalCentral South UniversityChangsha 410008China
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2022年第14卷第12期
页 面：1-16页
核心收录：
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学]
基 金：supported by grants from the National Natural Science Foundation of China(31930035,91942311,and 32061143028 to B.S.,32100730 to S.L.,32200738 to Y.C.,82071856 to L.L.) the National Key R&D Program of China(2021YFA1301400 to B.S.,2020YFA0113101 to L.L.) Shanghai Science and Technology Commission(20410714000,20JC410100,and 22JC1402600to B.S.,22490760400 to L.L.) Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases(to B.S.),Shanghai Municipal Commission of Health,Scientific Research Program of Traditional Chinese Medicine(2020jP009 to L.L.) Nurture Projects for Basic Research of Shanghai Chest Hospital(2021YNJCQ6 to X.0.) China Postdoctoral Science Foundation(2019M661550 to X.0.,2022T150422 to Y.C.) the National Postdoctoral Program for Innovative Talent(BX2021188 to S.L.) Y.C.wasan Innovation Program Postdoctoral Fellow and YuHe Postdoctoral Fellow at Shanghai Institute of Immunology Y.C.is also supported by fellowships from Shanghai Postdoctoral Excellence Progra
主 题：T lineage tracing Treg neonatal thymus-derived T cells neonatal thymus-derived Treg single-cell RNA sequencing
摘 要：It is well documented that the neonatal thymus-derived (neonatal-TD) regulatory T cells (Treg) are essential to prevent lethal autoimmune diseases and allergies, and neonatal and adult thymus possesses distinct output potentials for naïve T cells, including Treg. However, the molecular features and detailed functional differences between neonatal-TD and adult thymus-derived (adult-TD) T cells in terms of their ability to maintain immune homeostasis during long-term environmental influences are still largely unknown, partially due to the lack of appropriate animal models to precisely trace these cells at specific time points. In this study, neonatal-TD and adult-TD CD4+ T cells from the spleen and Peyer s patches were traced for 9 weeks by a T cell origin-time tracing mouse model and analysed by single-cell RNA sequencing. More Treg but fewer naïve T cells were found in neonatal-TD CD4+ T cells from both tissues than those from adult-TD counterparts. Interestingly, the neonatal-TD Treg in both the spleen and Peyer s patches exhibited augmented expression of Foxp3, Gata3, Ctla4, Icos, Il2ra, Tgfb1, and Nrp1, as well as enriched Gene Ontology terms like T cell activation and tolerance induction, indicating an enhanced immunosuppressive function. These results were further confirmed by flow cytometry analysis and in vitro immune suppression assays. Flow cytometry also revealed a significantly higher proportion of neonatal-TD Treg in total Treg than that of adult-TD counterparts, suggesting the longer lifespan of neonatal-TD Treg. To investigate the intrinsic features of neonatal-TD and adult-TD CD4+ T cells, a shortened tracing time was performed. Surprisingly, the neonatal-TD and adult-TD CD4+ T cells had similar proportions of Treg and did not exhibit significant differences in Foxp3, Gata3, Ctla4, Icos, Il2ra, and Tgfb1 expression levels after tracing for 12 days. On the other hand, neonatal-TD Treg present an increased Nrp1 expression level compared with adult-TD co
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