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Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer (cancer I)
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.