Cell function and activity is 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 reveling 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 a novel Arg1+ Trem2+ regulatory myeloid cell (Mreg) and identifies markers, metabolic activity and pathways associated with these cells. Genetic ablation of Trem2 in mice inhibits the 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. SOURCE: Ido Amit (ido.amit@weizmann.ac.il) -  Weizmann Institute of Science

Pluto Bioinformatics

GSE150876 (human): Coupled single cell RNA-seq and intracellular protein activity reveals immune-suppressive role of Trem2 in cancer II