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Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer
Ist Teil von
Cell, 2020-08, Vol.182 (4), p.872-885.e19
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2020
Quelle
Elsevier ScienceDirect Journals
Beschreibungen/Notizen
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 intra-cellular maps and identifies the molecular signature of myeloid suppressive cells in tumors.
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•INs-seq: a new technology for recording scRNA-seq and intracellular protein activity•INs-seq defines new immune subsets by TF combinations and metabolic activity•Mapping Arg1+ cells within tumors reveals novel Trem2+ suppressive myeloid cells•Genetic ablation of Trem2 decreases Mreg, exhausted CD8+ T cells and tumor growth
INs-seq, an integrated technology for scRNA-seq and intracellular protein activity uncovers a novel Arg1+ Trem2+ regulatory myeloid cells (Mreg), genetic ablation of Trem2 inhibits the accumulation of intra-tumoral Mreg, leading to immune reactivation and reduced tumor growth.