Similar Datasets
Project description:A complete chart of the chromatin regulatory elements of immune cells in patients with cancer and their dynamic behavior is necessary to understand the developmental fates and guide therapeutic strategies. Here, we map the single-cell chromatin landscape of immune cells from blood, normal tumor-adjacent kidney tissue and malignant tissue from patients with early-stage clear cell renal cell carcinoma (ccRCC). We catalog the T cell states dictated by tissue-specific and developmental-stage-specific chromatin accessibility patterns, infer key chromatin regulators and observe rewiring of regulatory networks in the progression to dysfunction in CD8+ T cells. Unexpectedly, among the transcription factors orchestrating the path to dysfunction, NF-κB is associated with a pro-apoptotic program in late stages of dysfunction in tumor-infiltrating CD8+ T cells. Importantly, this epigenomic profiling stratified ccRCC patients based on a NF-κB-driven pro-apoptotic signature. This study provides a rich resource for understanding the functional states and regulatory dynamics of immune cells in ccRCC.
| S-EPMC9325682 | biostudies-literature
Project description:A complete chart of the chromatin regulatory elements of immune cells in patients with cancer and their dynamic behavior is necessary to understand the developmental fates and to guide therapeutic strategies. Here, we map, at the single-cell level, the chromatin landscape of immune cells from blood, normal adjacent kidney, and malignant tissue from patients with early-stage clear cell renal cell carcinoma (ccRCC). Specifically in T cells, we catalogue the various cell states dictated by tissue- and developmental stage-specific chromatin accessibility patterns and we infer key chromatin regulators of these states. In the CD8+ T cells progression to dysfunction, we observe an extensive rewiring of the regulatory networks. Unexpectedly, we find that among the transcription factors that orchestrate the path to dysfunction, NFkB, a transcription factor with an established prosurvival role during TCR-mediated activation, is associated with a proapoptotic program in late stages of dysfunction in ccRCC infiltrating CD8+ T cells. Importantly, the epigenomic profiling can stratify RCC patients based on a NFkB-driven proapoptotic signature which was also validated at the gene expression and protein level. Our study provides a rich resource for understanding the functional states and regulatory dynamics of immune cells in RCC.
2021-12-31 | GSE181062 | GEO
Project description:A complete chart of the chromatin regulatory elements of immune cells in patients with cancer and their dynamic behavior is necessary to understand the developmental fates and to guide therapeutic strategies. Here, we map, at the single-cell level, the chromatin landscape of immune cells from blood, normal adjacent kidney, and malignant tissue from patients with early-stage clear cell renal cell carcinoma (ccRCC). Specifically in T cells, we catalogue the various cell states dictated by tissue- and developmental stage-specific chromatin accessibility patterns and we infer key chromatin regulators of these states. In the CD8+ T cells progression to dysfunction, we observe an extensive rewiring of the regulatory networks. Unexpectedly, we find that among the transcription factors that orchestrate the path to dysfunction, NFkB, a transcription factor with an established prosurvival role during TCR-mediated activation, is associated with a proapoptotic program in late stages of dysfunction in ccRCC infiltrating CD8+ T cells. Importantly, the epigenomic profiling can stratify RCC patients based on a NFkB-driven proapoptotic signature which was also validated at the gene expression and protein level. Our study provides a rich resource for understanding the functional states and regulatory dynamics of immune cells in RCC.
2021-12-31 | GSE181061 | GEO
Project description:A single-cell map of dynamic chromatin landscapes of immune cells in renal cell carcinoma
| PRJNA750487 | ENA
Project description:A single-cell map of dynamic chromatin landscapes of immune cells in renal cell carcinoma (scATAC-Seq)
| PRJNA750490 | ENA
Project description:A single-cell map of dynamic chromatin landscapes of immune cells in renal cell carcinoma (scRNA-Seq and TCR-Seq)
| PRJNA750491 | ENA
Project description:Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here, we assess the performance of a massively parallel droplet-based method for mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq). We apply scATAC-seq to obtain chromatin profiles of more than 200,000 single cells in human blood and basal cell carcinoma. In blood, application of scATAC-seq enables marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity and reconstruction of trajectories of cellular differentiation. In basal cell carcinoma, application of scATAC-seq reveals regulatory networks in malignant, stromal and immune cells in the tumor microenvironment. Analysis of scATAC-seq profiles from serial tumor biopsies before and after programmed cell death protein 1 blockade identifies chromatin regulators of therapy-responsive T cell subsets and reveals a shared regulatory program that governs intratumoral CD8+ T cell exhaustion and CD4+ T follicular helper cell development. We anticipate that scATAC-seq will enable the unbiased discovery of gene regulatory factors across diverse biological systems.
| S-EPMC7299161 | biostudies-literature
Project description:The aim of our research is to explore the various characteristics and genetic profiles of clear cell renal cell carcinoma (ccRCC) in order to discover possible predictors of prognosis and targets for treatment. By utilizing ssGSEA scores, we categorized patients with ccRCC into groups based on their phenotype, distinguishing between low and high. This categorization revealed significant variations in the expression of crucial immune checkpoint genes and Human Leukocyte Antigen (HLA) genes, suggesting the presence of a potential immune evasion tactic in different subtypes of ccRCC. A predictive model was built using genes that are expressed differently and linked to cell death, showing strong effectiveness in categorizing patient risk. Furthermore, we discovered a noteworthy correlation among risk scores, infiltration of immune cells, the expression of genes related to immune checkpoint inhibitors, and diverse clinical features. This indicates that our scoring system for risk could function as a comprehensive gauge of the severity of the disease. The examination of the mutational terrain further highlighted the predominance of particular genetic changes, including VHL and PBRM1 missense mutations. Finally, we have discovered the function of DKK1 in facilitating cell death in ccRCC, presenting an additional possibility for therapeutic intervention. The results of our study suggest the possibility of incorporating molecular information into clinical prediction, which could lead to personalized treatment approaches in ccRCC.
| S-EPMC10577421 | biostudies-literature
Project description:Clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high response rate to immunotherapies, despite low tumor mutational burden. To characterize the tumor immune microenvironment of ccRCC, we applied single-cell-RNA sequencing (SCRS) along with T-cell-receptor (TCR) sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45+ lymphoid and myeloid cells in matched tumor and blood from three patients with ccRCC. We also included 11,367 immune cells from four other individuals derived from the kidney and peripheral blood to facilitate the identification and assessment of ccRCC-specific differences. There is an overall increase in CD8+ T-cell and macrophage populations in tumor-infiltrated immune cells compared to normal renal tissue. We further demonstrate the divergent cell transcriptional states for tumor-infiltrating CD8+ T cells and identify a MKI67 + proliferative subpopulation being a potential culprit for the progression of ccRCC. Using the SCRS gene expression, we found preferential prediction of clinical outcomes and pathological diseases by subcluster assignment. With further characterization and functional validation, our findings may reveal certain subpopulations of immune cells amenable to therapeutic intervention.
| S-EPMC7840906 | biostudies-literature
Project description:T cells play a critical role in coronavirus diseases. How they do so in COVID-19 may be revealed by analyzing the epigenetic chromatin accessibility of cis- and trans-regulatory elements and creating transcriptomic immune profiles. We performed single-cell assay for transposase-accessible chromatin (scATAC) and single-cell RNA (scRNA) sequencing (seq) on the peripheral blood mononuclear cells (PBMCs) of severely ill/critical patients (SCPs) infected with COVID-19, moderate patients (MPs), and healthy volunteer controls (HCs). About 76,570 and 107,862 single cells were used, respectively, for analyzing the characteristics of chromatin accessibility and transcriptomic immune profiles by the application of scATAC-seq (nine cases) and scRNA-seq (15 cases). The scATAC-seq detected 28,535 different peaks in the three groups; among these peaks, 41.6 and 10.7% were located in the promoter and enhancer regions, respectively. Compared to HCs, among the peak-located genes in the total T cells and its subsets, CD4+ T and CD8+ T cells, from SCPs and MPs were enriched with inflammatory pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway and tumor necrosis factor (TNF) signaling pathway. The motifs of TBX21 were less accessible in the CD4+ T cells of SCPs compared with those in MPs. Furthermore, the scRNA-seq showed that the proportion of T cells, especially the CD4+ T cells, was decreased in SCPs and MPs compared with those in HCs. Transcriptomic results revealed that histone-related genes, and inflammatory genes, such as NFKBIA, S100A9, and PIK3R1, were highly expressed in the total T cells, CD4+ T and CD8+ T cells, both in the cases of SCPs and MPs. In the CD4+ T cells, decreased T helper-1 (Th1) cells were observed in SCPs and MPs. In the CD8+T cells, activation markers, such as CD69 and HLA class II genes (HLA-DRA, HLA-DRB1, and HLA-DRB5), were significantly upregulated in SCPs. An integrated analysis of the data from scATAC-seq and scRNA-seq showed some consistency between the approaches. Cumulatively, we have generated a landscape of chromatin epigenetic status and transcriptomic immune profiles of T cells in patients with COVID-19. This has provided a deeper dissection of the characteristics of the T cells involved at a higher resolution than from previously obtained data merely by the scRNA-seq analysis. Our data led us to suggest that the T-cell inflammatory states accompanied with defective functions in the CD4+ T cells of SCPs may be the key factors for determining the pathogenesis of and recovery from COVID-19.
| S-EPMC7943924 | biostudies-literature