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- W4293577933 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 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. Human 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. Here, 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. Our 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 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. Our 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." @default.
- W4293577933 created "2022-08-30" @default.
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- W4293577933 date "2022-01-01" @default.
- W4293577933 modified "2023-10-16" @default.
- W4293577933 title "Culture-Associated DNA Methylation Changes Impact on Cellular Function of Human Intestinal Organoids" @default.
- W4293577933 cites W1483496013 @default.
- W4293577933 cites W1741548448 @default.
- W4293577933 cites W1965157206 @default.
- W4293577933 cites W1969941116 @default.
- W4293577933 cites W1974047233 @default.
- W4293577933 cites W1984562049 @default.
- W4293577933 cites W1988075836 @default.
- W4293577933 cites W1988903229 @default.
- W4293577933 cites W1991059160 @default.
- W4293577933 cites W2002513358 @default.
- W4293577933 cites W2019214599 @default.
- W4293577933 cites W2020541351 @default.
- W4293577933 cites W2024819383 @default.
- W4293577933 cites W2045949302 @default.
- W4293577933 cites W2069377300 @default.
- W4293577933 cites W2074448914 @default.
- W4293577933 cites W2085652695 @default.
- W4293577933 cites W2085683078 @default.
- W4293577933 cites W2099042456 @default.
- W4293577933 cites W2101870168 @default.
- W4293577933 cites W2102093038 @default.
- W4293577933 cites W2102659607 @default.
- W4293577933 cites W2107665951 @default.
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- W4293577933 cites W2117398145 @default.
- W4293577933 cites W2124317383 @default.
- W4293577933 cites W2125154191 @default.
- W4293577933 cites W2129915465 @default.
- W4293577933 cites W2139077902 @default.
- W4293577933 cites W2143149122 @default.
- W4293577933 cites W2145825942 @default.
- W4293577933 cites W2148521032 @default.
- W4293577933 cites W2151591434 @default.
- W4293577933 cites W2151829259 @default.
- W4293577933 cites W2156564520 @default.
- W4293577933 cites W2158261276 @default.
- W4293577933 cites W2198641185 @default.
- W4293577933 cites W2207084272 @default.
- W4293577933 cites W2323326409 @default.
- W4293577933 cites W2480728253 @default.
- W4293577933 cites W2529024004 @default.
- W4293577933 cites W2587150600 @default.
- W4293577933 cites W2620721366 @default.
- W4293577933 cites W2762883136 @default.
- W4293577933 cites W2770282900 @default.
- W4293577933 cites W2771057425 @default.
- W4293577933 cites W2771076222 @default.
- W4293577933 cites W2785550069 @default.
- W4293577933 cites W2795164082 @default.
- W4293577933 cites W2888002084 @default.
- W4293577933 cites W2890909528 @default.
- W4293577933 cites W2911418673 @default.
- W4293577933 cites W2914004989 @default.
- W4293577933 cites W294850324 @default.
- W4293577933 cites W2950896295 @default.
- W4293577933 cites W2991775683 @default.
- W4293577933 cites W2993993303 @default.
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- W4293577933 doi "https://doi.org/10.1016/j.jcmgh.2022.08.008" @default.
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