科學家繪製出小鼠和人類αβT細胞發育的表觀基因組和轉錄組整合圖譜
作者：
小柯機器人發布時間：2020/11/27 14:20:02
近日，美國國立衛生研究院Rémy Bosselut及其小組繪製出小鼠和人類αβT細胞發育的表觀基因組和轉錄組整合圖譜。該研究於2020年11月25日在線發表於國際一流學術期刊《免疫》。
通過結合單細胞RNA和ATAC（染色質可及性）測序，研究人員確定了小鼠和人類αβ胸腺細胞的發育軌跡。研究人員證明了CD4+和CD8+譜系的不對稱出現，激動劑信號細胞的分化程序與其MHC特異性相匹配，並鑑定了小鼠和人類轉錄組和表觀基因組模式之間的對應關係。通過對CD4+譜系轉錄因子Thpok的單細胞數據和結合位點的計算分析，研究人員推斷出與CD4+或CD8+譜系分化以及Thpok或CD8+譜系Runx3的表達相關的轉錄網絡。
這些發現為CD4+和CD8+T細胞分化的機制提供了見識，並為αβT細胞發育的機制研究奠定了基礎。
據了解，αβ譜系T細胞（大多數是CD4+或CD8+，並識別MHC I或MHC II呈遞的抗原）對於免疫應答至關重要，並從CD4+CD8+胸腺細胞發育而來。目前體外模型的缺乏和αβ胸腺細胞的異質性阻礙了胸腺內分化的分析。
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