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Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer (cancer II - mouse)
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, and Ido Amit
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 intracellular maps and identifies the molecular signature of myeloid suppressive cells in tumors.