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Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity.
Cell ( IF 45.5 ) Pub Date : 2019-10-24 , DOI: 10.1016/j.cell.2019.09.035 Chrysothemis C Brown 1 , Herman Gudjonson 2 , Yuri Pritykin 3 , Deeksha Deep 4 , Vincent-Philippe Lavallée 3 , Alejandra Mendoza 4 , Rachel Fromme 4 , Linas Mazutis 3 , Charlotte Ariyan 5 , Christina Leslie 3 , Dana Pe'er 3 , Alexander Y Rudensky 5
Cell ( IF 45.5 ) Pub Date : 2019-10-24 , DOI: 10.1016/j.cell.2019.09.035 Chrysothemis C Brown 1 , Herman Gudjonson 2 , Yuri Pritykin 3 , Deeksha Deep 4 , Vincent-Philippe Lavallée 3 , Alejandra Mendoza 4 , Rachel Fromme 4 , Linas Mazutis 3 , Charlotte Ariyan 5 , Christina Leslie 3 , Dana Pe'er 3 , Alexander Y Rudensky 5
Affiliation
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Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood. By combining transcriptional and chromatin analyses with genetic reporter expression, we identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORγt, two key transcription factors known to define innate and adaptive lymphocyte subsets. These novel cDC2 lineages were characterized by distinct metabolic and functional programs. Extending our findings to humans revealed conserved DC heterogeneity and the presence of the newly defined cDC2 subsets in human cancer.
中文翻译：
小鼠和人类树突状细胞异质性的转录基础。
树突状细胞（DC）在协调适应性免疫反应中起着至关重要的作用，因为它们具有启动T细胞反应并将其分化为效应子谱系的独特能力。基于表型标记及其对CD8和CD4 T细胞的独特能力，经典DC已分为cDC1和cDC2两个子集。虽然已经很好地描述了cDC1子集的转录调控，但是对cDC2的发育和功能的了解仍然很少。通过将转录和染色质分析与遗传报告基因表达相结合，我们确定了两个主要的cDC2谱系，这些谱系由不同的发育途径和转录调节因子定义，包括T-bet和RORγt，这是两个已知的定义固有和适应性淋巴细胞亚群的关键转录因子。这些新颖的cDC2谱系的特征在于独特的代谢和功能程序。将我们的发现扩展至人类发现了保守的DC异质性以及人类癌症中新定义的cDC2亚型的存在。
更新日期：2019-11-09
中文翻译：
小鼠和人类树突状细胞异质性的转录基础。
树突状细胞（DC）在协调适应性免疫反应中起着至关重要的作用，因为它们具有启动T细胞反应并将其分化为效应子谱系的独特能力。基于表型标记及其对CD8和CD4 T细胞的独特能力，经典DC已分为cDC1和cDC2两个子集。虽然已经很好地描述了cDC1子集的转录调控，但是对cDC2的发育和功能的了解仍然很少。通过将转录和染色质分析与遗传报告基因表达相结合，我们确定了两个主要的cDC2谱系，这些谱系由不同的发育途径和转录调节因子定义，包括T-bet和RORγt，这是两个已知的定义固有和适应性淋巴细胞亚群的关键转录因子。这些新颖的cDC2谱系的特征在于独特的代谢和功能程序。将我们的发现扩展至人类发现了保守的DC异质性以及人类癌症中新定义的cDC2亚型的存在。
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