生物
细胞内
转录因子
特雷姆2
髓样
表观遗传学
癌症研究
信号转导
癌细胞
细胞生物学
癌症
基因
计算生物学
遗传学
免疫系统
髓系细胞
作者
Yonatan Katzenelenbogen,Fadi Sheban,Adam Yalin,Ido Yofe,Dmitry Svetlichnyy,Diego Adhemar Jaitin,Chamutal Bornstein,Adi Moshe,Hadas Keren‐Shaul,Michal Cohen,Shuang-Yin Wang,Baoguo Li,Eyal David,Tomer-Meir Salame,Assaf Weiner,Ido Amit
出处
期刊:Cell
[Elsevier]
日期:2020-08-01
卷期号:182 (4): 872-885.e19
被引量:292
标识
DOI:10.1016/j.cell.2020.06.032
摘要
Cell function and activity are regulated through integration of signaling, epigenetic, transcriptional, and metabolic pathways. Here, we introduce INs-seq, an integrated technology for massively parallel recording of single-cell RNA sequencing (scRNA-seq) and intracellular protein activity. We demonstrate the broad utility of INs-seq for discovering new immune subsets by profiling different intracellular signatures of immune signaling, transcription factor combinations, and metabolic activity. Comprehensive mapping of Arginase 1-expressing cells within tumor models, a metabolic immune signature of suppressive activity, discovers novel Arg1+ Trem2+ regulatory myeloid (Mreg) cells and identifies markers, metabolic activity, and pathways associated with these cells. Genetic ablation of Trem2 in mice inhibits accumulation of intra-tumoral Mreg cells, leading to a marked decrease in dysfunctional CD8+ T cells and reduced tumor growth. This study establishes INs-seq as a broadly applicable technology for elucidating integrated transcriptional and intra-cellular maps and identifies the molecular signature of myeloid suppressive cells in tumors.
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