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EECS, UC Berkeleyhttps://www.ebi.ac.uk/ena/browser/view/PRJNA302460Mus musculusExtensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or polarized in vitro under either pathogenic or non-pathogenic differentiation conditions. Computational analysis reveals a spectrum of cellular states in vivo, including a self-renewal state, Th1-like effector/memory states and a dysfunctional/senescent state. Relating these states to in vitro differentiated Th17 cells, unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four novel genes: Gpr65, Plzp, Toso and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity, and can identify targets for selective suppression of pathogenic Th17 cells while sparing non-pathogenic tissue-protective ones. Overall design: Single-cell transcriptional profiling of Th17 cells, harvested at peak of disease in EAE from LNENAother disease, d230, GFP cell, Allergic Encephalomyelitis, experimental autoimmune encephalomyelitis, dTAFII250, Ctla-8, EfW1, dmTAF[[II]]230, EAE, diseases, dmTAF1, Taf230, GFP 细胞, disease or disorder, diseases and disorders, TH-17 Cells, Allergic encephalomyelitis, IL-17, Experimental allergic encephalomyelitis (disorder), Autoimmune, TAF250, Taf200, human disease, dTAF[[II]]250, T Helper 17 Cells, TFIID TAF250, cel, cell, Type 17 Helper T Cell, Allergic, GFP, Autoimmune Experimental, Taf1p, TH-17 Cell, non-neoplastic, dTAF250, NICR1047., Type 17 Helper T Cells, AUTOIMMUNE ENCEPH EXPER, disorder, Homo sapiens disease, EXPER ALLERGIC ENCEPH, TAF, Experimental Allergic Encephalomyelitis, ENCEPH EXPER AUTOIMMUNE, Cytotoxic T-lymphocyte-associated antigen 8, dTAF[[II]]230, TAF[[II]]250, CTLA8, ALLERGIC ENCEPH, Experimental Allergic Encephalomyelitides, Autoimmune Encephalomyelitis, Il17, disorders, TAF200, l(3)84Ab, ALLERGIC ENCEPH EXPER, Th17 Cell, BG:DS00004.13, medical condition, TAFII-250, TAF250/230, Cell, Th17, dTAF230, TAFII250, Experimental, TH 17 Cells, IL17, p230, Diseases, Experimental Autoimmune, TAF[[II]]250/230, Experimental Encephalomyelitis, TFIID, condition, EXPER AUTOIMMUNE ENCEPH, Taf[[II]]250, Encephalomyelitis, Experimental Allergic, CTLA-8, TAF[[II]]230, ENCEPH ALLERGIC, Ctla8, TAF[II]250, CG17603, TAF[[II]], Allergic encephalomyelitis (disorder), TH 17 Cell, TH-17, disease, ENCEPH AUTOIMMUNE EXPER, IL-17A, DmelCG17603, Taf250, SR3-5, Cells, AUTOIMMUNE EXPER ENCEPH, T Helper 17 Cell, TAF230, TAF1, Autoimmune Experimental Encephalomyelitismouse, mouse <Mus musculus>, house mouse.0.00.00.00.00.00falseMus musculusSingle-cell transcriptional profiling of Th17 cells, harvested at peak of disease in EAE from LN [EAE-LN-IL-17A/GFP+]2022-05-122015-11-22PRJNA302460GSE75108311971582660779410090