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Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients [scRNA-seq]

ABSTRACT: Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients [scRNA-seq]

PROVIDER: PRJNA1011312 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25844800.fastq.gz	Fastqsanger.gz
	SRR25844801.fastq.gz	Fastqsanger.gz
	SRR25844802.fastq.gz	Fastqsanger.gz
	SRR25844803.fastq.gz	Fastqsanger.gz
	SRR25844804.fastq.gz	Fastqsanger.gz

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Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients

Project description:Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients

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Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients [scRNA-seq]

Project description:Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard treatment for patients with severe treatment resistant ulcerative colitis (UC). Despite significant improvements in patient outcomes, up to 50% of patients will develop inflammation of the pouch (pouchitis) within 1-2 years following surgery. The pathogenesis of pouchitis is not well understood. Functionalization of UC pouches is associated with histological changes, whether these reflect changes in cellular identity and metaplasia remains unclear. To address this question, we generated cellular atlases of single-cell transcriptomes and accessible chromatin to assess the cellular composition, transcriptomic and epigenetic profiles in UC pouches.

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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.

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