Persistent Inflammation of the Rectum in Perianal-Fisulizing Crohn's Disease Associates with Goblet Cell Function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA934333 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23446035_1.fastq.gz | Fastqsanger.gz | |||
| SRR23446035_2.fastq.gz | Fastqsanger.gz | |||
| SRR23446036_1.fastq.gz | Fastqsanger.gz | |||
| SRR23446036_2.fastq.gz | Fastqsanger.gz | |||
| SRR23446037_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 62 |
Similar Datasets
Project description:Perianal Fistulizing Crohn’s Disease (perianal-CD) is a debilitating form of CD typically associated with prolonged periods of morbidity. Leveraging single-cell RNA sequencing, rectal mucosal tissue was sequenced from individuals following anti-TNF biologic therapy having either active perianal-CD and inflamed rectal mucosa or healed perianal-CD but non-inflamed mucosa. Single cell transcriptomic profiles of the inflamed and non-inflamed tissue were contrasted to test for specific cellular subsets of rectal epithelial and immune cell compartments associated with inflamed perianal disease. We identified eight broad classes of epithelial, six of immune, and a small population of stromal cells in the rectal mucosa. There was an increase in colonocytes in the non-inflamed tissue compared to the inflamed tissue, and an increase of naïve b cells and plasma cells associated with inflamed tissue. The cell type proportions of immune cells, highlighted patient heterogeneity of cell type abundance and potential dysregulation of both the immune and epithelial compartment. We also note enrichment of IgG plasma cells in inflamed tissue of two donors and expansion of IgA plasma cells of non-inflamed tissue in two donors. Differential gene expression analysis of goblet cells revealed enrichment of inflammatory pathways, such as IL6 and interferon gamma signaling, in inflamed tissue. These inflammatory pathways might affect tight junctions between epithelial cells leading to increased permeability and potentially affect fistula formation. Our findings suggest dysregulation of crypt maturation during persistent inflammation and over-abundance of goblet cells and colonocyte precursors in inflamed tissue of perianal-CD.
2023-02-20 | GSE225199 | GEO
Project description: Not available
| S-EPMC11307797 | biostudies-literature
Project description:Using isolation stress model, we showed that goblet cell-dependent mucosal barrier functions in the mouse rectum was more vulnerable to stress than the colon. We also found that isolation stress specifically stimulated IL-18 production only in the rectum. Furthermore, the crucial role of IL-18 in the stress response of the mouse rectum was confirmed using IL-18 knockout mice. Microarray analysis was used to assess the stress response and to identify responsible genes for the vulnerability of the mouse rectum to isolation stress.
2009-02-14 | GSE11910 | GEO
Project description:Using isolation stress model, we showed that goblet cell-dependent mucosal barrier functions in the mouse rectum was more vulnerable to stress than the colon. We also found that isolation stress specifically stimulated IL-18 production only in the rectum. Furthermore, the crucial role of IL-18 in the stress response of the mouse rectum was confirmed using IL-18 knockout mice. Microarray analysis was used to assess the stress response and to identify responsible genes for the vulnerability of the mouse rectum to isolation stress. Experiment Overall Design: Total RNA was prepared from the colon and the rectum of wild-type and IL-18 knockout mice before isolation and 8 days after starting isolation. The one GSM sample of microarray analysis was made by pooling an equal amount of total RNA 5 mice of each group. Agilent whole mouse genome oligonucleotide microarray was used to measure gene expression in these samples according to the manufactureâ??s protocol.
2009-02-26 | E-GEOD-11910 | biostudies-arrayexpress
Project description:Background and aims: Perianal fistulizing Crohn’s disease (CD) is severe and often more difficult to treat than luminal CD. Current therapeutics focusing solely on the immune system neither target epithelial and mesenchymal compartments nor consider genetic/epigenetic mechanisms, potentially missing causative aspects of the disease. Thus, the mucosal cells and organoids from a cohort of perianal fistulizing CD patients and controls with diverse genetic backgrounds were experimentally examined. Results: Overall, 140,503 mucosa and 77,044 organoid cells were sequenced. Inflamed perianal CD showed changes across the mucosal compartments (epithelium, immune, stromal), the most dramatic taking place in the epithelium. Epithelial changes occurring in the rectum of perianal CD patients associated with inflammation, gender, and ancestry, and were accompanied by a reduction in differentiated lineages. Organoids from the patient cohort retained both the gender- and ancestral-specific gene expression but did not overwhelmingly reflect their disease status. Organoids lacked bona fide differentiated lineages, but secretory pathways were promoted through PGE2-PTGER4 signaling and HDAC function. Conclusion: Epigenetic modifications are disrupted in the epithelium during inflammation and perianal fistulizing CD that affect the differentiation capacity of those cells, limiting their production/function and thus diminishing the ability of the patients’ mucosal tissue to heal. These epigenetic modifications appear to be modulated by crosstalk between the epithelial and mesenchymal cells, and thus might be leveraged therapeutically.
2024-11-22 | GSE256497 | GEO
Project description:Escherichia coli strain:rectum | isolate:rectum Genome sequencing
| PRJNA1031530 | ENA
Project description:Crohn’s disease (CD) is a chronic inflammatory condition that can affect any part of the gastrointestinal tract. African ancestry (AA) populations have been substantially under-represented in genome-wide association studies (GWAS) of CD and inflammatory bowel disease (IBD), reflecting in part the lower prevalence of CD in AA compared to European ancestry (EA) populations. Importantly, CD complicated by perianal fistulae has been found to be more prevalent and severe in African-ancestry patients. Perianal fistulae arise from the distal rectal mucosa and can course to a cutaneous surface, resulting in highly morbid complications. Monoclonal antibodies against anti-TNF are the mainstay of treatment, but recurrence and secondary loss-of-response is common. In severe, uncontrolled cases, complete proctectomy is required. The intestine is unique among adult tissues in that under homeostasis, residential macrophages are continually replenished from recruited blood monocytes. In EA cohorts, we established that chronic monocyte cultures stimulated with NOD2 agonists result in aberrant myeloid-stromal differentiation stratified by risk allele carrier status. NOD2 risk alleles are not associated with perianal fistulae; African-American patients with CD do not carry them (except via recent European ancestry admixture). There is no direct association between known CD GWAS risk loci and the risk of developing perianal fistula. Here, we present direct ex-vivo, single cell multiomic analyses of colorectal tissues and perianal fistulous tracts in AA and EA cases to define mechanisms of perianal fistula development. We implicate myeloid-stromal crosstalk and define cell subtypes using single cell RNA (scRNASeq), ATAC sequencing, and chronic, unstimulated monocyte cultures. Transcription factor motifs and ATAC signals co-localized with fine-mapped GWAS loci provide insight to cell-specific and transcriptional network regulation.
2024-05-16 | GSE260833 | GEO
Project description:We have demonstrated that the colon and rectum are transcriptionally distinct in mice and that the colon can be differentiated from rectum based on microarray profiles. This transition occurs over the first weeks of life, indicating environmental exposure is an important mediator.
2012-08-20 | GSE38753 | GEO
Project description:Crohn’s disease (CD) is a chronic inflammatory condition that can affect any part of the gastrointestinal tract. African ancestry (AA) populations have been substantially under-represented in genome-wide association studies (GWAS) of CD and inflammatory bowel disease (IBD), reflecting in part the lower prevalence of CD in AA compared to European ancestry (EA) populations. Importantly, CD complicated by perianal fistulae has been found to be more prevalent and severe in African-ancestry patients. Perianal fistulae arise from the distal rectal mucosa and can course to a cutaneous surface, resulting in highly morbid complications. Monoclonal antibodies against anti-TNF are the mainstay of treatment, but recurrence and secondary loss-of-response is common. In severe, uncontrolled cases, complete proctectomy is required. The intestine is unique among adult tissues in that under homeostasis, residential macrophages are continually replenished from recruited blood monocytes. In EA cohorts, we established that chronic monocyte cultures stimulated with NOD2 agonists result in aberrant myeloid-stromal differentiation stratified by risk allele carrier status. NOD2 risk alleles are not associated with perianal fistulae; African-American patients with CD do not carry them (except via recent European ancestry admixture). There is no direct association between known CD GWAS risk loci and the risk of developing perianal fistula. Here, we present direct ex-vivo, single cell multiomic analyses of colorectal tissues and perianal fistulous tracts in AA and EA cases to define mechanisms of perianal fistula development. We implicate myeloid-stromal crosstalk and define cell subtypes using single cell RNA (scRNASeq), ATAC sequencing, and chronic, unstimulated monocyte cultures. Transcription factor motifs and ATAC signals co-localized with fine-mapped GWAS loci provide insight to cell-specific and transcriptional network regulation.
2024-05-16 | GSE260842 | GEO
Project description:High numbers of goblet cells in airways contribute to the mucus obstruction characteristic of asthmatic airways. Allergen challenged mice exhibit robust expression of goblet cells within airway surface epithelium. This study looks at the temporal analysis of IL-13 exposed murine airways to elucidate pathways that result in differentiation of airway epithelial cells to goblet cells.
2008-06-13 | E-GEOD-481 | biostudies-arrayexpress