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Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
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Patient-derived Colonoids From Disease-spared Tissue Retain Inflammatory Bowel Disease-specific Transcriptomic
Tatiana A Karakasheva1, Yusen Zhou1,2, Hongbo M Xie2
1Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Gastro Hep Advances
|September 22, 2023
Summary
Human enteroids and colonoids accurately reflect transcriptional differences in Crohn disease. This validates their use in studying inflammatory bowel disease and identifying disease status from unaffected tissue.
Area of Science:
- Gastroenterology
- Molecular Biology
- Translational Medicine
Background:
- Inflammatory bowel disease (IBD) is characterized by mucosal damage and epithelial barrier disruption.
- Human enteroids and colonoids serve as vital bench-to-bedside models for investigating IBD's epithelial aspects.
- This study aimed to identify sustained transcriptional differences between healthy and IBD subjects in these models, even using disease-spared tissue.
Purpose of the Study:
- To define and confirm transcriptional differences in patient-derived enteroids and colonoids compared to healthy controls.
- To assess if these transcriptional signatures are maintained in vitro.
- To evaluate the potential of these models for diagnosing IBD and identifying disease characteristics.
Main Methods:
- RNA sequencing was performed on biopsies and matching enteroid/colonoid cultures from pediatric Crohn disease patients and controls.
- Bioinformatic and machine learning analyses were employed to identify differential gene expression patterns.
- Late-passage enteroids were treated with cytokines to assess the durability of transcriptional changes.
Main Results:
- Significant overlap was observed in upregulated pathways between Crohn disease biopsies and corresponding enteroids/colonoids.
- Key upregulated KEGG pathways included cytokine-cytokine receptor interaction, chemokine signaling, and Toll-like receptor signaling.
- Machine learning models accurately predicted biopsy location and donor disease status, with ileal enteroid data predicting Crohn disease in rectal colonoids.
Conclusions:
- Transcriptional profiles of Crohn disease biopsies are reliably recapitulated in patient-derived enteroids and colonoids.
- Transcriptomic data from disease-spared tissue can identify patients with Crohn disease, highlighting the models' translational potential.
- Patient-derived enteroids and colonoids are validated as critical tools for IBD research and drug development.
