Single-cell single-molecule spatial transcriptomics using CosMx on colectomy specimens collected during Pouch surgery in IBD patients.
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ABSTRACT:
PROVIDER: PRJNA1194636 | ENA |
REPOSITORIES: ENA
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Project description:Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to considerable morbidity. This retrospective case-control study aimed to identify histopathological features of the TAC specimen associated with subsequent pouch failure and to investigate the underlying molecular mechanisms of this susceptibility using single-cell spatial transcriptomics.
2025-02-26 | GSE283625 | GEO
Project description:IBD CosMx NanoString data from colonic mucosa
| PRJNA982807 | ENA
Project description:Inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory diseases with increasing worldwide prevalence that show a perplexing heterogeneity in manifestations and response to treatment. We applied spatial transcriptomics at single-cell resolution (CosMx Spatial Molecular Imaging) to human inflamed and uninflamed intestine.
2023-06-13 | GSE234713 | GEO
Project description:Spatial transcriptomics is a rapidly growing field with the potential to enhance our ability to uncover novel biology, support drug development, and guide biomarker discovery. However, a biologically validated comparison of leading single-cell-level spatial transcriptomics platforms to guide scientists is lacking in the field. Using intestinal biopsies (n = 40) from patients with inflammatory bowel disease (IBD) of varying disease states and disease locations and non-diseased controls, we systematically compared two imaging based spatial transcriptomics platforms (CosMx and Xenium) to guide translational work for two NIDDK supported IBD consortiums and the Crohn’s and Colitis Foundation Plexus Biorepository. In vitro experiments were conducted to validate key biologic findings. We present a comprehensive data resource of over 1.5 million spatially profiled intestinal cells from healthy and IBD samples. We observed CosMx to have overall better data quality than Xenium in both ulcerative colitis and Crohn’s disease across the full spectrum of commercially available panels. The performance of Xenium, but not CosMx, was significantly influenced by block quality and panel size, with a decline in data quality as the panel size increased. We demonstrate operational feasibility for CosMx in multi-center studies, and CosMx uniquely identified Treg-associated biology in both ulcerative colitis and Crohn’s disease which was validated by in vitro experiments. This study highlights the performance differences between CosMx and Xenium, demonstrating the strengths of CosMx for biology discovery in IBD research. Further studies are needed to explore the broader applicability of CosMx in other gastrointestinal conditions.
2026-03-13 | GSE312415 | GEO
Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes. In order to determine how host gene expression might influence, or be influenced by the tissue associated microbiome, we analyzed 205 IPAA patients with biopsies collected from the pouch and afferent limb for host transcriptomics and 16S rDNA gene sequencing. Metadata included antibiotic use, inflammation score, and clinical classification. To achieve power for a genome-wide microbiome-transcriptome association study, we used principal component analysis to reduce OTUs and host transcripts to eigengenes and eigenclades explaining 50% of observed variance. These were subsequently tested for significant covariation with one another and/or outcome using multivariate linear modeling.
2015-01-27 | E-GEOD-65270 | biostudies-arrayexpress
Project description:Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized in response to inflammation and to develop mechanistic hypotheses of pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing. We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n=15) and without an ileal pouch-anal anastomosis (n=11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify drug targets for patients with inflamed pouches. We identified a population of IL1B+ antimicrobial macrophages and FOXP3+/BATF+ T cells that are expanded in inflamed tissues, which we further validated in other single cell RNA-seq datasets from IBD patients. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressing IL1B with S100A8/A9 calprotectin as being associated with inflammation, and Bacteroidiales and Clostridiales bacterial taxa. We found that non-responsiveness to anti-integrin biologic therapies in ulcerative colitis patients was associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions. Specifically, we relate inflammation of the pouch, a surgically constructed organ, to other inflammatory contexts throughout the gastrointestinal tract.
2020-12-01 | GSE162335 | GEO
Project description:The pathophysiology of Crohn’s-like disease of the pouch (CDP) that develops after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single cell analyses.
2024-08-02 | GSE246987 | GEO
Project description:UC pouchitis is a potential model of UC. We prospectively examined the pouch transcriptomes of UC and familial adenomatous polyposis (FAP) IPAA patients to unveil molecular mechanisms of UC pouchitis susceptibility. Methods: Total RNA was isolated using the AllPrep DNA/RNA Mini Kit (QIAGEN, Cat No. 8020). RNA quality was evaluated using Bioanalyzer (Agilent, Santa Clara, CA). All RNA samples displayed RNA Integrity Number (RIN) >7. RNAseq including cDNA library preparation was processed at the Genomics Core Facility of University of Chicago (https://fgf.uchicago.edu/). Total RNA in the amount of 100-500μg per sample was depleted of ribosomal RNA using the Ribo-Zero kit (Epicentre, Madison, WI). The directional (first strand) cDNA libraries were prepared following the guide of TruSeq Stranded Total RNA Sample Preparation kit. Results: Unlike FAP patients, UC subjects exhibited a large set of differentially expressed genes (DEGs) between pouch and pre-pouch mucosa as early as 4 months after pouch functionalization. Functional pathway analysis of DEGs in UC pouch revealed: (1) Gain of colon-associated gene expressions and loss of ileum associated gene expressions, (2) enhanced state of immune/inflammatory response, and (3) suppressed xenobiotic, lipid, and bile acid metabolic pathways. These changes were corroborated upon reanalysis of a published larger cross-sectional study of UC and FAP patients. Moreover, >70% of DEGs mapped to published IBD and normal colonic microarray datasets displayed directional changes consistent with active UC, but not Crohn's disease. Conclusions: UC patients exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease. The transcriptome alterations provide insights into pouchitis
2016-05-11 | GSE81266 | GEO
Project description:The human kidneys are comprised of multiple different cell types in a complex anatomical arragemnt that is optimal for their key functions such as waste removal, regulation of fluid and electrolyte homeostasis and production of hormones. In chronic kidney disease (CKD) this arrangement is disrupted with de-differentiation and atrophy of epithelial cells, recruitment of immune cells and activation of myofibroblasts to produce excess scarring. A better understanding of cellular phenotypes, complex intercellular communication and intracellular signaling pathways that promote CKD could lead to development of novel therapies. We applied single-cell spatial transcriptomics (CosMx Spatial molecular imaging) to human kidney neprectomy speciemens with unilateral ureteral obstruction (UUO, n=5) and healthy kidneys (n=2).
2025-03-20 | GSE282059 | GEO
Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes.
2015-01-27 | GSE65270 | GEO