生物
表观遗传学
CD8型
转录因子
主要组织相容性复合体
细胞分化
胸腺细胞
谱系(遗传)
细胞生物学
转录组
T细胞
染色质
遗传学
计算生物学
DNA甲基化
抗原
免疫系统
基因
基因表达
作者
Laura B. Chopp,Vishaka Gopalan,Thomas Ciucci,Allison Ruchinskas,Zachary Rae,Manon Lagarde,Yayi Gao,Caiyi Li,Marita Bosticardo,Francesca Pala,Ferenc Livak,Michael C. Kelly,Sridhar Hannenhalli,Remy Bosselut
出处
期刊:Immunity
[Elsevier]
日期:2020-12-01
卷期号:53 (6): 1182-1201.e8
被引量:41
标识
DOI:10.1016/j.immuni.2020.10.024
摘要
αβ lineage T cells, most of which are CD4+ or CD8+ and recognize MHC I- or MHC II-presented antigens, are essential for immune responses and develop from CD4+CD8+ thymocytes. The absence of in vitro models and the heterogeneity of αβ thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human αβ thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4+ and CD8+ lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. Through computational analysis of single-cell data and binding sites for the CD4+-lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4+- or CD8+-lineage differentiation, and with expression of Thpok or of the CD8+-lineage factor Runx3. Our findings provide insight into the mechanisms of CD4+ and CD8+ T cell differentiation and a foundation for mechanistic investigations of αβ T cell development.
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