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Induced organoids derived from patients with ulcerative colitis recapitulate the colitic reactivity

ABSTRACT: Induced organoids derived from patients with ulcerative colitis recapitulate the colitic reactivity

PROVIDER: PRJNA641142 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12070655.fastq.gz	Fastqsanger.gz
	SRR12070656.fastq.gz	Fastqsanger.gz
	SRR12070657.fastq.gz	Fastqsanger.gz
	SRR12070658.fastq.gz	Fastqsanger.gz
	SRR12070659.fastq.gz	Fastqsanger.gz

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Induced organoids derived from patients with ulcerative colitis recapitulate the colitic reactivity

Project description:We report the application of single nucleus RNA-seq technology for transcriptomic-wide profiling of the induced organoids derived from patients with ulcerative colitis (iHUCO) and normal induced organoids derived from the healthy colon (iHNO), along with their parental fibroblasts. By comapring the nucleus profiles of both iHUCOs and their parental fibroblasts (UC FBs) to iHNOs and normal fibroblasts (NL FBs), we found unique signatures exclusive to the UC samples but not the controls. We also report that UC FBs and iHUCOs share the layers of similarities in their single nucleus profile. This study provides a framework for the application of the induced patient-derived organoids as a more comprehensive model to study human UC.

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Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity.

Project description:The pathogenesis of ulcerative colitis (UC), a major type of inflammatory bowel disease, remains unknown. No model exists that adequately recapitulates the complexity of clinical UC. Here, we take advantage of induced pluripotent stem cells (iPSCs) to develop an induced human UC-derived organoid (iHUCO) model and compared it with the induced human normal organoid model (iHNO). Notably, iHUCOs recapitulated histological and functional features of primary colitic tissues, including the absence of acidic mucus secretion and aberrant adherens junctions in the epithelial barrier both in vitro and in vivo. We demonstrate that the CXCL8/CXCR1 axis was overexpressed in iHUCO but not in iHNO. As proof-of-principle, we show that inhibition of CXCL8 receptor by the small-molecule non-competitive inhibitor repertaxin attenuated the progression of UC phenotypes in vitro and in vivo. This patient-derived organoid model, containing both epithelial and stromal compartments, will generate new insights into the underlying pathogenesis of UC while offering opportunities to tailor interventions to the individual patient.

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Project description:Ulcerative colitis related gene expressions analysis in colonic biopsy samples from control and ulcerative colitis patients

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Project description:The series was designed to identify the different methylated single CpGs involved in the pathophysiology of ulcerative colitis. A cohort of n=20 monozygotic twins, discordant for ulcerative colitis was selected. Illumina and Nimblegen platforms were used.

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Project description:Through laser capture microdissection and microarray analysis combined with slightly modified RNA extraction and amplification. we could analyze the subtle differential expression between colon normal cell and ulcerative colitis. Keywords: Ulcerative Colitis, amplification, microdissection

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Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Experiment Overall Design: The series contain eight UC samples with macroscopic signs of inflammation, 13 UC smaples without macroscopic signs of inflammation, five control subjects.

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