| First Author | Katzenelenbogen Y | Year | 2020 |
| Journal | Cell | Volume | 182 |
| Issue | 4 | Pages | 872-885.e19 |
| PubMed ID | 32783915 | Mgi Jnum | J:305204 |
| Mgi Id | MGI:6705761 | Doi | 10.1016/j.cell.2020.06.032 |
| Citation | Katzenelenbogen Y, et al. (2020) Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer. Cell 182(4):872-885.e19 |
| abstractText | 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. |
