Single-cell RNA-seq and single-cell ATAC-seq of in vitro polarized mouse Th17 and T1h cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206175 | GEO | 2023/06/01
REPOSITORIES: GEO
Similar Datasets
Project description: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 in vitro polarized Th17 cells, either sorted for IL17A/GFP+ or unsorted.
2015-11-20 | E-GEOD-75103 | biostudies-arrayexpress
Project description: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. Single-cell transcriptional profiling of Th17 cells, differentiated in vitro for 48h
2015-11-20 | E-GEOD-75110 | biostudies-arrayexpress
Project description:CD4+ T cells can differentiate into multiple effector subsets but the potential roles of these subsets in anti-tumor immunity have not been fully explored. We sought to study the impact of CD4+ T cell polarization on efficacy of tumor rejection in a model closely mimicking human disease where the target antigens are often non-mutated tissue differentiation self-antigens. We generated a new transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen that is expressed by normal melanocytes and B16 murine melanoma. We found that cells could be robustly polarized into Th0, Th1 and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles as well as by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells play the most important role in tumor rejection, we found that Th17-polarized cells were superior in mediating destruction of advanced B16 melanoma. Unexpectedly, their therapeutic effect was critically dependent on IFN-γ production, while depletion of IL-17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for the successful tumor eradication. This principle should be taken under consideration in the design of future clinical trials involving adoptive transfer-based immunotherapy of human malignancies. Two-condition experiment: RNA from TRP-1 transgenic mouse lymphocytes polarized to be either Th1 or Th17 were compared to cells polarized to be Th0. Keywords: Lymphocyte polarization comparison Comparative analysis of gene expression changes observed when murine lymphocytes are differentially in vitro polarized .
2010-05-25 | E-GEOD-10814 | biostudies-arrayexpress
Project description:To understand the molecular programs driving Th17 heterogeneity and CD4 T cell fate, we profiled in vitro polarized non-pathogenic Th17, pathogenic Th17, Th1, and Treg cells using RNA-seq.
2023-06-01 | GSE206304 | GEO
Project description:To understand the molecular programs driving Th17 heterogeneity and ATAC CD4 T cell fate, we profiled in vitro polarized non-pathogenic Th17, pathogenic Th17, Th1, and Treg cells using ATAC-seq.
2023-06-01 | GSE206607 | GEO
Project description: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. Single-cell transcriptional profiling of Th17 cells, differentiated in vitro for 48h
2015-11-20 | E-GEOD-75109 | biostudies-arrayexpress
Project description: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. Single-cell transcriptional profiling of Th17 cells, differentiated in vitro for 48h
2015-11-20 | E-GEOD-75111 | biostudies-arrayexpress
Project description: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.
2015-11-20 | GSE75103 | GEO
Project description:CD4+ T cells can differentiate into multiple effector subsets but the potential roles of these subsets in anti-tumor immunity have not been fully explored. We sought to study the impact of CD4+ T cell polarization on efficacy of tumor rejection in a model closely mimicking human disease where the target antigens are often non-mutated tissue differentiation self-antigens. We generated a new transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen that is expressed by normal melanocytes and B16 murine melanoma. We found that cells could be robustly polarized into Th0, Th1 and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles as well as by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells play the most important role in tumor rejection, we found that Th17-polarized cells were superior in mediating destruction of advanced B16 melanoma. Unexpectedly, their therapeutic effect was critically dependent on IFN-γ production, while depletion of IL-17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for the successful tumor eradication. This principle should be taken under consideration in the design of future clinical trials involving adoptive transfer-based immunotherapy of human malignancies. Two-condition experiment: RNA from TRP-1 transgenic mouse lymphocytes polarized to be either Th1 or Th17 were compared to cells polarized to be Th0. Keywords: Lymphocyte polarization comparison
2008-03-15 | GSE10814 | GEO
Project description: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.
2015-11-20 | GSE75110 | GEO