Population transcriptional profiling of KO or WT cells,, differentiated in vitro for 48-96h towards Th17 cells

ABSTRACT: Extensive 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. Population transcriptional profiling of KO or WT cells,, differentiated in vitro for 48-96h towards Th17 cells

OTHER RELATED OMICS DATASETS IN: PRJNA302459 PRJNA302463 PRJNA302454 PRJNA302462 PRJNA302465 PRJNA302461 PRJNA302460 PRJNA302457 PRJNA302458 PRJNA302464

ORGANISM(S): Mus Musculus

SUBMITTER: Nir Yosef   Jellert Gaublomme  Aviv Regev 

PROVIDER: E-GEOD-75104 | ArrayExpress | 2015-11-20

SECONDARY ACCESSION(S): GSE75104SRP066313PRJNA302464

REPOSITORIES: GEO, ArrayExpress, ENA