ArticleCellular and molecular gastroenterology and hepatology2022
Culture-Associated DNA Methylation Changes Impact on Cellular Function of Human Intestinal Organoids.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Guiding Principles: Reporting Elements for Gastrointestinal Organoid Research.Cellular and molecular gastroenterology and hepatology · 2026Guideline
- Current smoking and COPD are associated with differentiation-dependent secretory and inflammatory programs in airway basal cells.Respiratory research · 2026Article
- Interplay of the ENS and Microbiota With Murine Gut Epithelium-Derived Organoids in Aging.Aging cell · 2026Article
- Culture-specific transcriptional drifts limit the fidelity of organoid infection models.PLoS pathogens · 2026Article
- Epigenetic biomarkers in inflammatory bowel diseases-computational challenges and opportunities.Journal of Crohn's & colitis · 2026Review
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- Advances in liver and pancreas organoids: how far we have come and where we go next.Nature reviews. Gastroenterology & hepatology · 2026Review
- Intestinal Stem Cells From Patients With Inflammatory Bowel Disease Retain an Epigenetic Memory of Inflammation.Cellular and molecular gastroenterology and hepatology · 2026Article
- RESTRICT-seq enables time-gated CRISPR screens and uncovers novel epigenetic dependencies of SCC resistance.bioRxiv : the preprint server for biology · 2025Article
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- An integrated transcriptomic cell atlas of human endoderm-derived organoids.Nature genetics · 2025Article
- The Circulating Methylome in Childhood-Onset Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2025Article
- The application of explants, crypts, and organoids as models in intestinal barrier research.Tissue barriers · 2025Article
- Apical-out bovine intestinal organoids as an infection model forCurrent research in parasitology & vector-borne diseases · 2025Article
- Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Article
- A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening.Cell reports methods · 2024Article
- Prolonged culturing of colonic epithelial organoids derived from healthy individuals and ulcerative colitis patients results in the decrease of LINE-1 methylation level.Scientific reports · 2024Article
- Bridging the gap: advancing cancer cell culture to reveal key metabolic targets.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsHuman intestinal epithelial organoids (IEOs) are a powerful tool to model major aspects of intestinal development, health, and diseases because patient-derived cultures retain many features found in vivo. A necessary aspect of the organoid model is the requirement to expand cultures in vitro through several rounds of passaging. This is of concern because the passaging of cells has been shown to affect cell morphology, ploidy, and function.
methodsHere, we analyzed 173 human IEO lines derived from the small and large bowel and examined the effect of culture duration on DNA methylation (DNAm). Furthermore, we tested the potential impact of DNAm changes on gene expression and cellular function.
resultsOur analyses show a reproducible effect of culture duration on DNAm in a large discovery cohort as well as 2 publicly available validation cohorts generated in different laboratories. Although methylation changes were seen in only approximately 8% of tested cytosine-phosphate-guanine dinucleotides (CpGs) and global cellular function remained stable, a subset of methylation changes correlated with altered gene expression at baseline as well as in response to inflammatory cytokine exposure and withdrawal of Wnt agonists. Importantly, epigenetic changes were found to be enriched in genomic regions associated with colonic cancer and distant to the site of replication, indicating similarities to malignant transformation.
conclusionsOur study shows distinct culture-associated epigenetic changes in mucosa-derived human IEOs, some of which appear to impact gene transcriptomic and cellular function. These findings highlight the need for future studies in this area and the importance of considering passage number as a potentially confounding factor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.