BioProject

Cell function and activity is regulated through integration of signaling, epigenetic, transcriptional and metabolic pathways. More...

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. Overall design: 9 different 10x experiments were done, with 20 samples in total. No repeats. Less...