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鼠标和人类树突细胞异质性的转录基础

Chrysothemis C Brown¹, Herman Gudjonson², Yuri Pritykin³

¹Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.

|November 1, 2019

概括

研究人员发现了两种新的树突细胞 (cDC2a和cDC2b),对免疫反应至关重要. 这些通过高级分析识别的独特的DC子集具有独特的发育路径和功能,为适应性免疫和癌症提供了新的见解.

科学领域:

免疫学
细胞生物学
转录法规

背景情况:

树突细胞 (DCs) 是适应性免疫的关键协调者,启动T细胞反应.
经典的DC包括cDC1和cDC2子集,cDC1的转录调节已得到充分研究,但cDC2的发展和功能仍然不太清楚.

研究的目的:

阐明古典树突细胞子集2 (cDC2) 的发展和功能.
识别cDC2种群中的不同血统及其调节机制.

主要方法:

综合转录分析和染色体分析.
使用基因记者表达来追踪DC的发展.
对物种进行比较分析以确定保存机制.

主要成果:

确定了两个主要的cDC2谱系,具有不同的发育途径.
发现了新的转录调节剂,包括T-bet和RORγt,定义了这些cDC2系.
对每个新的cDC2子集进行独特的代谢和功能程序.
在人类癌症样本中确认了这些保存的cDC2子集的存在.

结论:

树突细胞的异质性超出了先前定义的子集.
由T-bet和RORγt调节的两个新型cDC2系表现出不同的功能程序.
这些发现揭示了人类保存的DC多样性以及对理解癌症免疫反应的含义.

关键词:

ATAC 测序一个T-bet 树突细胞骨髓状细胞单细胞RNA测序转录调节

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