Similar Datasets
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.
2024-01-22 | GSE250490 | GEO
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.
2024-01-22 | GSE250488 | GEO
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.
2024-01-22 | GSE250487 | GEO
Project description:Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis
| PRJNA1054155 | ENA
Project description:Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis [biopsy scRNA-seq]
| PRJNA1054148 | ENA
Project description:Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis [blood scRNA-seq]
| PRJNA1054167 | ENA
Project description:Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis [biopsy CITE-seq]
| PRJNA1054168 | ENA
Project description:The mammalian nucleus is compartmentalized by diverse subnuclear structures. These subnuclear structures, marked by nuclear bodies and histone modifications, are often cell-type specific and affect gene regulation and 3D genome organization 1-3 . Understanding nuclear organization requires identifying the molecular constituents of subnuclear structures and mapping their associations with specific genomic loci in individual cells, within complex tissues. Here, we introduce two-layer DNA seqFISH+, which allows simultaneous mapping of 100,049 genomic loci, together with nascent transcriptome for 17,856 genes and a diverse set of immunofluorescently labeled subnuclear structures all in single cells in cell lines and adult mouse cerebellum. Using these multi-omics datasets, we showed that repressive chromatin compartments are more variable by cell type than active compartments. We also discovered a single exception to this rule: an RNA polymerase II (RNAPII)-enriched compartment was associated with long, cell-type specific genes (> 200kb), in a manner distinct from nuclear speckles. Further, our analysis revealed that cell-type specific facultative and constitutive heterochromatin compartments marked by H3K27me3 and H4K20me3 are enriched at specific genes and gene clusters, respectively, and shape radial chromosomal positioning and inter-chromosomal interactions in neurons and glial cells. Together, our results provide a single-cell high-resolution multi-omics view of subnuclear compartments, associated genomic loci, and their impacts on gene regulation, directly within complex tissues.
| S-EPMC10197539 | biostudies-literature
Project description:The mammalian nucleus is compartmentalized by diverse subnuclear structures. These subnuclear structures, marked by nuclear bodies and histone modifications, are often cell-type specific and affect gene regulation and 3D genome organization. Understanding nuclear organization and its role in gene expression requires identifying the molecular constituents of subnuclear structures and mapping their associations with specific genomic loci and their transcriptional levels in individual cells, within complex tissues. Here, we introduce two-layer DNA seqFISH+, which allows simultaneous mapping of 100,049 genomic loci, together with nascent transcriptome for 17,856 genes and a diverse set of immunofluorescently labeled subnuclear structures all in single cells in both cell lines and complex tissues. These data enable imaging-based chromatin profiling of diverse subnuclear markers and capture changes in chromatin organization at genomic scales from 100–200 kb to approximately 1 Mb, depending on the subnuclear marker and DNA locus. Using multi-omics datasets in the adult mouse cerebellum, we showed that repressive chromatin regions are more variable by cell type than active regions across the genome. We also discovered RNA polymerase II (RNAPII)-enriched foci were locally associated with long, cell-type specific genes (> 200kb), in a manner distinct from nuclear speckles. Further, our analysis revealed that cell-type specific facultative and constitutive heterochromatin regions marked by H3K27me3 and H4K20me3 are enriched at specific genes and gene clusters, respectively, and shape radial chromosomal positioning and inter-chromosomal interactions in neurons and glial cells. Together, our results provide a single-cell high-resolution multi-omics view of subnuclear structures and chromatin marks, associated genomic loci, and their impacts on gene regulation, directly within complex tissues.
2024-12-21 | GSE248631 | GEO
Project description:Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.
| S-EPMC8852248 | biostudies-literature