Similar Datasets
Project description:Spatial transcriptomic signatures of cardiac sarcoidosis
| PRJNA1393118 | ENA
Project description:Cardiac involvement is an important determinant of mortality amongst sarcoidosis patients. While granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain unresolved. Furthermore, it is unclear how the cellular and transcriptomic landscape of cardiac sarcoidosis differs from other inflammatory heart diseases. We leveraged spatial transcriptomics (GeoMx DSP) and single nucleus RNA sequencing (snRNAseq) to elucidate the cellular and transcriptional landscape of cardiac sarcoidosis. Using GeoMX DSP technology, we compared the transcriptomal profile of CD68+ rich immune cell infiltrates in human cardiac sarcoidosis, giant cell myocarditis, and lymphocytic myocarditis. We performed snRNAseq of human cardiac sarcoidosis to identify immune cell types and examined their transcriptomic landscape and regulation. Using multi-channel immunofluorescence staining, we validated immune cell populations identified by snRNAseq, determined their spatial relationship, and devised an immunostaining approach to distinguish cardiac sarcoidosis from other inflammatory heart diseases. Despite overlapping histological features, spatial transcriptomics identified transcriptional signatures and associated pathways that robustly differentiated cardiac sarcoidosis from giant cell myocarditis and lymphocytic myocarditis. snRNAseq revealed the presence of diverse populations of myeloid cells in cardiac sarcoidosis with distinct molecular features. We identified GPNMB as a novel marker of multinucleated giant cells and predicted that the MITF family of transcription factors regulated this cell type. We also detected additional macrophage populations in cardiac sarcoidosis including HLA-DR+ macrophages, SYTL3+ macrophages and CD163+ resident macrophages. HLA-DR+ macrophages were found immediately adjacent to GPMMB+ giant cells, a distinct feature compared with other inflammatory cardiac diseases. SYTL3+ macrophages were located scattered throughout the granuloma and CD163+ macrophages, CD1c+ dendritic cells, non-classical monocytes, and T-cells were located at the periphery and outside of the granuloma. Finally, we demonstrate mTOR pathway activation is associated with proliferation and is selectively found in HLA-DR+ and SYLT3+ macrophages. In this study, we identified diverse populations of immune cells with distinct molecular signatures that comprise the sarcoid granuloma. These findings provide new insights into the pathology of cardiac sarcoidosis and highlight opportunities to improve diagnostic testing.
2022-07-01 | GSE205734 | GEO
Project description:We performed Visium CytAssist (10X), GeoMx DSP (Nanostring) and Chromium Flex (10X Genomics) full transcriptome profiling on Breast Cancer (BC), Lung Cancer (LC) and diffuse large B cell lymphoma (DLBCL) samples from archival FFPE blocks. We explore the data quality across blocks with different storage times and DV200 values for all the three methods. We compared the cell type signature purity between ST methods Visium and GeoMx by utilising pathology annotations and scRNAseq. For the Visium and Chromium methods with a large number of data points we explored the heterogeneity between tissues. Finally, we demonstrate the discovery of patient-specific tumor-TME interactions across all three methods.
2024-11-01 | E-MTAB-14566 | biostudies-arrayexpress
Project description:Transcriptional and immune landscape of cardiac sarcoidosis
| PRJNA847259 | ENA
Project description:We performed Visium CytAssist (10X), GeoMx DSP (Nanostring) and Chromium Flex (10X Genomics) full transcriptome profiling on Breast Cancer (BC), Lung Cancer (LC) and diffuse large B cell lymphoma (DLBCL) samples from archival FFPE blocks. We explore the data quality across blocks with different storage times and DV200 values for all the three methods. We compared the cell type signature purity between ST methods Visium and GeoMx by utilising pathology annotations and scRNAseq. For the Visium and Chromium methods with a large number of data points we explored the heterogeneity between tissues. Finally, we demonstrate the discovery of patient-specific tumor-TME interactions across all three methods.
2024-11-01 | E-MTAB-14560 | biostudies-arrayexpress
Project description:Comparing 10x Visium spatial transcriptomic technologies
| PRJNA1071205 | ENA
Project description:Human uterine samples were analysed using Visium technology (10X Genomics) to generate a cellular 2D map of the endometrium to study its temporal and spatial changes across the menstrual cycle. Dataset comprises 4 samples from two women in their reproductive age.
2021-08-17 | E-MTAB-9260 | biostudies-arrayexpress
Project description:Sarcoidosis is a multisystemic disease characterized by non-caseating granuloma infiltrating various organs. The form with symptomatic muscular involvement is called muscular sarcoidosis. The impact of immune cells composing the granuloma on the skeletal muscle is misunderstood. Here, we investigated the granuloma-skeletal muscle interactions through spatial transcriptomics. Five major transcriptomic clusters corresponding to perigranuloma, granuloma, and three successive muscle tissue areas (proximal, intermediate and distal) around the granuloma were identified. Analyses revealed upregulated pathways in the granuloma corresponding to the activation of T-lymphocytes and monocytes/macrophages cytokines and upregulation of extracellular matrix signatures and induction of the TGF-β signaling in the perigranuloma. Comparison between proximal and distal muscles to the granuloma revealed an inverse correlation between distance to the granuloma and upregulation of cellular response to interferon-γ/α, TNF-α, IL-1,4,6, fibroblast proliferation, epithelial to mesenchymal cell transition and downregulation of muscle gene expression. These data shed light on the intercommunications between granulomas and the muscle tissue and provides pathophysiological mechanisms by showing that granuloma immune-cells have a direct impact on proximal muscle tissue by promoting its progressive replacement by fibrosis via the expression of pro-inflammatory and pro-fibrosing signatures. These data could possibly explain the evolution towards a state of disability for some patients.
2023-11-29 | GSE243291 | GEO
Project description:Myocarditis is a severe inflammatory cardiac disease that can progress to dilated cardiomyopathy and heart failure. Experimental autoimmune myocarditis (EAM) represents an animal model of acute myocarditis, which is followed by the development of post-inflammatory cardiac fibrosis and systolic dysfunction. In this model, cardiac inflammation is characterized by the massive influx of myeloid infiltrates and is paralleled by the activation of extracellular matrix-producing cardiac fibroblasts. 6–8-week-old BALB/c mice were immunized with αMyHC peptide together with Complete Freunds’ Adjuvant to induce EAM. Heart tissues were isolated, embedded in OTC, sectioned into 10 µm-thick fragments, and placed on a 10x Genomics Visium Gene Expression Slide. Single-cell spatial libraries were prepared using 10x Genomics Visium protocols, and the sequencing was performed using Illumina Chemistry. Single-cell RNA sequencing data was analyzed using RStudio software. In our analysis, we included three biological time points: a healthy heart (d0), acute myocarditis (d19). Following sequencing, we analyzed 3789 spots under the tissue. We identified the main cell populations present in the mouse heart, including fibroblasts, immune cells, endothelial cells, smooth muscle cells, and cardiomyocytes. Subset analysis on cardiac fibroblasts resulted in the presence of four different subsets (FB1–FB6). Subset FB3 has a myofibroblastic signature defined by the expression of, among others, Acta2, Postn, Vim, Col1a1 and Col3a1. This subset is transiently present at d19 of EAM. Spatial analysis of infiltrating immune cells characterized by the expression of, e.g., Ly6c1 and Lyz2 resulted in the presence of five subsets (INF1–INF5). The INF4 subset is present only at acute myocarditis phase (d19) and is spatiotemporally colocalized with the myofibroblastic subset(FB3). Our data indicate that myofibroblasts and infiltrating immune cells colocalize within the tissue during acute phase of myocarditis. This may indicate active molecular interplay between inflammatory cells and cardiac fibroblasts.
2025-11-21 | GSE248347 | GEO
Project description:Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a gene signature distinguishing sarcoidosis from healthy controls, which also served as a molecular signature for complicated sarcoidosis.
2012-07-01 | GSE37912 | GEO