新方法揭示TREM2在癌症免疫抑制中的功能 作者： 发布时间：/8/13 16:26:47 以色列威兹曼科学研究所Ido Amit和Assaf Weiner团队合作取得一项新突破。他们利用scRNA-Seq和细胞内蛋白活性的耦合，揭示了TREM2在肿瘤免疫抑制中的功能。相关论文在线发表在8月11日出版的《细胞》杂志上。
研究人员研发了INs-seq，这是一种用于大规模平行记录单细胞RNA测序（scRNA-seq）和细胞内蛋白质活性的集成技术。通过分析免疫信号传导、转录因子组合和代谢活性的细胞内差异，研究人员证明了INs-seq在发现新免疫子集方面的广泛用途。通过对肿瘤模型中表达精氨酸酶1细胞（具有抑制活性的代谢免疫信号）的全面分析，研究人员发现了新型Arg1+ Trem2+调节性髓样（Mreg）细胞，并鉴定了分子标记、代谢活性和与这些细胞相关的通路。
在小鼠中利用遗传方法敲出Trem2抑制了肿瘤内Mreg细胞的积累，导致功能异常CD8+ T细胞显著减少，并抑制肿瘤生长。这项研究表明INs-seq是可用于阐明整合转录和细胞内图谱的广泛应用技术，并鉴定了肿瘤中髓样抑制细胞的分子标记。
据了解，细胞功能和活性受到信号传导、表观遗传、转录和代谢途径的整合调控。
附：英文原文
Title: Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer
Author: Yonatan Katzenelenbogen, Fadi Sheban, Adam Yalin, Ido Yofe, Dmitry Svetlichnyy, Diego Adhemar Jaitin, Chamutal Bornstein, Adi Moshe, Hadas Keren-Shaul, Merav Cohen, Shuang-Yin Wang, Baoguo Li, Eyal David, Tomer-Meir Salame, Assaf Weiner, Ido Amit
Issue Volume: -08-11
Abstract: Cell function and activity are regulated through integration of signaling, epigenetic,transcriptional, and metabolic pathways. Here, we introduce INs-seq, an integratedtechnology for massively parallel recording of single-cell RNA sequencing (scRNA-seq)and intracellular protein activity. We demonstrate the broad utility of INs-seq fordiscovering new immune subsets by profiling different intracellular signatures ofimmune signaling, transcription factor combinations, and metabolic activity. Comprehensivemapping of Arginase 1-expressing cells within tumor models, a metabolic immune signatureof suppressive activity, discovers novel Arg1+ Trem2+ regulatory myeloid (Mreg) cells and identifies markers, metabolic activity, and pathwaysassociated with these cells. Genetic ablation of Trem2 in mice inhibits accumulationof 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 applicabletechnology for elucidating integrated transcriptional and intra-cellular maps andidentifies the molecular signature of myeloid suppressive cells in tumors.
DOI: 10.1016/j.cell..06.032
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期刊信息 Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216官方网址：投稿链接：
