Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

被引：423

作者：

Brown, Chrysothemis C. ^{[1
,2
,3
]}

Gudjonson, Herman ^{[3
]}

Pritykin, Yuri ^{[4
]}

Deep, Deeksha ^{[1
,2
]}

Lavallee, Vincent-Philippe ^{[4
]}

Mendoza, Alejandra ^{[1
,2
]}

Fromme, Rachel ^{[1
,2
]}

Mazutis, Linas ^{[4
]}

Ariyan, Charlotte ^{[1
,2
,5
]}

Leslie, Christina ^{[4
]}

Pe'er, Dana ^{[4
]}

Rudensky, Alexander Y. ^{[1
,2
,5
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Immunol Program, New York, NY 10065 USA

[3] UCL Great Ormond St Inst Child Hlth, Infect Inflammat & Rheumatol Sect, London WC1N 1EH, England

[4] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Computat & Syst Biol Program, New York, NY 10065 USA

[5] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, New York, NY 10065 USA

来源：

CELL | 2019年 / 179卷 / 04期

基金：

英国惠康基金;

关键词：

INNATE LYMPHOID-CELLS; REGULATORY T-CELLS; IN-VIVO DEPLETION; CHEMOKINE RECEPTOR; SIGNALING CONTROLS; READ ALIGNMENT; BONE-MARROW; EXPRESSION; DIFFERENTIATION; REVEALS;

D O I：

10.1016/j.cell.2019.09.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 ROR gamma t, 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.

引用

页码：846 / +

页数：42

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