ArticleCells2021
Epigenetic Drifts during Long-Term Intestinal Organoid Culture.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Guiding Principles: Reporting Elements for Gastrointestinal Organoid Research.Cellular and molecular gastroenterology and hepatology · 2026Guideline
- Placenta models for HIV-1-ART-nicotine comorbidity research: advances and remaining challenges.Cell death discovery · 2026Review
- Culture-specific transcriptional drifts limit the fidelity of organoid infection models.PLoS pathogens · 2026Article
- Characterization of jejunal enteroids in human obesity; a model for studying GLP-1 cells.International journal of obesity (2005) · 2026Article
- Tumor Assembloids as Three-Dimensional Platforms for Modeling Drug Delivery Barriers: Construction Strategies, Applications, and Translational Challenges.Drug design, development and therapy · 2026Review
- Review
- Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.Journal of translational medicine · 2025Review
- Scalable, compressed phenotypic screening using pooled perturbations.Nature biotechnology · 2025Article
- Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment.NPJ precision oncology · 2025Article
- Reconstructing the hepatocellular carcinoma microenvironment: the current status and challenges of 3D culture technology.Discover oncology · 2025Review
- Organoids in biliary research: insights into developmental signaling and applications in disease modeling.Frontiers in cell and developmental biology · 2025Review
- Patient-derived tumor organoids: advances, applications, and future directions in biomedical research.Frontiers in medicine · 2025Review
- Initial pig developmental stage influences intestinal organoid growth but not cellular composition.Animal models and experimental medicine · 2024Article
- Intestinal carcinogenicity screening of environmental pollutants using organoid-based cell transformation assay.Archives of toxicology · 2024Article
- Utilizing Patient-Derived Organoids in the Management of Colorectal Cancer with Peritoneal Metastases: A Review of Current Literature.Journal of gastrointestinal cancer · 2023Review
- Morphological alterations in C57BL/6 mouse intestinal organoids as a tool for predicting chemical-induced toxicity.Archives of toxicology · 2023Article
- Gene expression in organoids: an expanding horizon.Biology direct · 2023Review
- Organoid Cultures In Silico: Tools or Toys?Bioengineering (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Organoids retain the morphological and molecular patterns of their tissue of origin, are self-organizing, relatively simple to handle and accessible to genetic engineering. Thus, they represent an optimal tool for studying the mechanisms of tissue maintenance and aging. Long-term expansion under standard growth conditions, however, is accompanied by changes in the growth pattern and kinetics. As a potential explanation of these alterations, epigenetic drifts in organoid culture have been suggested. Here, we studied histone tri-methylation at lysine 4 (H3K4me3) and 27 (H3K27me3) and transcriptome profiles of intestinal organoids derived from mismatch repair (MMR)-deficient and control mice and cultured for 3 and 20 weeks and compared them with data on their tissue of origin. We found that, besides the expected changes in short-term culture, the organoids showed profound changes in their epigenomes also during the long-term culture. The most prominent were epigenetic gene activation by H3K4me3 recruitment to previously unmodified genes and by H3K27me3 loss from originally bivalent genes. We showed that a long-term culture is linked to broad transcriptional changes that indicate an ongoing maturation and metabolic adaptation process. This process was disturbed in MMR-deficient mice, resulting in endoplasmic reticulum (ER) stress and Wnt activation. Our results can be explained in terms of a mathematical model assuming that epigenetic changes during a long-term culture involve DNA demethylation that ceases if the metabolic adaptation is disturbed.
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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.