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

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

PROVIDER: PRJNA1011310 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25844700_1.fastq.gz	Fastqsanger.gz
	SRR25844700_2.fastq.gz	Fastqsanger.gz
	SRR25844701_1.fastq.gz	Fastqsanger.gz
	SRR25844701_2.fastq.gz	Fastqsanger.gz
	SRR25844702_1.fastq.gz	Fastqsanger.gz

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Project description:Background & aimsTotal proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard of care for patients with severe treatment resistant ulcerative colitis (UC). Despite improvements in patient outcomes, about 50% of patients will develop inflammation of the pouch within 1-2 years following surgery. Establishment of UC pouches is associated with profound histological changes of the mucosa. A detailed characterization of these changes on a cellular and molecular level is crucial for an improved understanding of pouch physiology and diseases management.MethodsWe generated cell-type-resolved transcriptional and epigenetic atlases of UC pouches using scRNA-seq and scATAC-seq data from paired biopsy samples from the ileal pouch and ileal segment above the pouch (pre-pouch) of UC-IPAA patients (n=6, female=2) without symptoms. We also collected data from paired biopsies of the terminal ileum (TI) and ascending colon (AC) from healthy controls (n=6, female=3).ResultsWe identified novel populations of colon-like absorptive and secretory epithelial cells, constituting a significant proportion of the epithelial cell fraction in the pouch but not in matched pre-pouch samples. Pouch-specific enterocytes expressed colon-specific genes, including CEACAM5, CA2. However, in contrast to normal colonic epithelium, these cells also expressed a range of inflammatory and secretory genes, similar to previously detected gene expression signatures in IBD patients. Comparison to longitudinal bulk RNA-seq data from UC pouches demonstrated that colon-like epithelial cells are present early after pouch functionalization and independently of subsequent pouchitis. Finally, single cell chromatin accessibility revealed activation colonic transcriptional regulators, including CDX1, NFIA, and EHF.ConclusionUC pouches are characterized by partial colonic metaplasia of the epithelium. These data constitute a resource of transcriptomic and epigenetic signatures of cell populations in the pouch and provide an anchor for understanding the underlying molecular mechanisms of pouchitis.

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

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