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科学家绘制出小鼠和人类αβT细胞发育的表观基因组和转录组整合图谱
作者:小柯机器人 发布时间:2020/11/27 14:20:02

近日,美国国立卫生研究院Rémy Bosselut及其小组绘制出小鼠和人类αβT细胞发育的表观基因组和转录组整合图谱。该研究于2020年11月25日在线发表于国际一流学术期刊《免疫》。

通过结合单细胞RNA和ATAC(染色质可及性)测序,研究人员确定了小鼠和人类αβ胸腺细胞的发育轨迹。研究人员证明了CD4+和CD8+谱系的不对称出现,激动剂信号细胞的分化程序与其MHC特异性相匹配,并鉴定了小鼠和人类转录组和表观基因组模式之间的对应关系。通过对CD4+谱系转录因子Thpok的单细胞数据和结合位点的计算分析,研究人员推断出与CD4+或CD8+谱系分化以及Thpok或CD8+谱系Runx3的表达相关的转录网络。
 
这些发现为CD4+和CD8+T细胞分化的机制提供了见识,并为αβT细胞发育的机制研究奠定了基础。
 
据了解,αβ谱系T细胞(大多数是CD4+或CD8+,并识别MHC I或MHC II呈递的抗原)对于免疫应答至关重要,并从CD4+CD8+胸腺细胞发育而来。目前体外模型的缺乏和αβ胸腺细胞的异质性阻碍了胸腺内分化的分析。
 
附:英文原文

Title: An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development

Author: 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, Rémy Bosselut

Issue&Volume: 2020-11-25

Abstract: αβ lineage T cells, most of which are CD4+ or CD8+ and recognize MHC I- or MHC II-presented antigens, are essential for immune responsesand develop from CD4+CD8+ thymocytes. The absence of in vitro models and the heterogeneity of αβ thymocytes have hampered analyses of their intrathymicdifferentiation. 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 MHCspecificity, and identified correspondences between mouse and human transcriptomicand epigenomic patterns. Through computational analysis of single-cell data and bindingsites for the CD4+-lineage transcription factor Thpok, we inferred transcriptional networks associatedwith 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 celldevelopment.

DOI: 10.1016/j.immuni.2020.10.024

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30465-9

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx