Cell, 2020-08, Vol.182 (4), p.872-885.e19
2020
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Details
- Autor(en) / Beteiligte
- Titel
- 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. [Display omitted] •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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0092-8674eISSN: 1097-4172DOI: 10.1016/j.cell.2020.06.032Titel-ID: cdi_proquest_miscellaneous_2434059474
- Format
- –
- Schlagworte
- Animals, Arginase - genetics, Arginase - metabolism, cancer immunology, CD8-Positive T-Lymphocytes - cytology, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Dendritic Cells - cytology, Dendritic Cells - drug effects, Dendritic Cells - metabolism, Female, fixation, Gene Expression Regulation, Humans, immunotherapy, intracellular staining, Leukocytes, Mononuclear - cytology, Leukocytes, Mononuclear - metabolism, Lipopolysaccharides - pharmacology, MDSC, Membrane Glycoproteins - genetics, Membrane Glycoproteins - metabolism, Mice, Mice, Inbred C57BL, myeloid suppressive cells, Neoplasms - immunology, Neoplasms - metabolism, Neoplasms - pathology, p38 Mitogen-Activated Protein Kinases, Receptors, Immunologic - genetics, Receptors, Immunologic - metabolism, RNA, Small Cytoplasmic - chemistry, RNA, Small Cytoplasmic - metabolism, scRNA-seq, Sequence Analysis, RNA, single cell genomics, Single-Cell Analysis, Transcription Factors - metabolism, Trem2, Tumor Microenvironment, Tumor Necrosis Factor-alpha - metabolism