Culture associated DNA methylation changes impact on cellular function of Human Intestinal Organoids (Methylation)
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Rachel Edgar
PROVIDER: E-MTAB-11545 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Human intestinal epithelial organoid models are rapidly emerging as novel experimental tools to investigate intestinal epithelial biology. A necessary aspect of organoid use is the passaging of cells and long term maintenance in culture. DNA methylation has been demonstrated to play a key role in regulating gene expression and cellular function. Here we explore the effect of culture duration on organoid DNA methylation. The experiment consists of genome-wide DNA methylation profiling by Infinium HumanMethylationEPIC BeadChip of intestinal organoid cultures from paediatric ileum and colon. Our genome wide DNA methylation datasets represent a unique resource, which can be used by other researchers to validate their model systems Note: Some samples in this data set were replicated from a previously submitted to ArrayExpress under accession number E-MTAB-4957. They're clearly marked in the “Description” field in sample annotations.
2022-08-31 | E-MTAB-9748 | biostudies-arrayexpress
Project description:Human intestinal epithelial organoids (IEO) culture models are rapidly emerging as novel experimental tools to investigate fundamental aspects of intestinal epithelial (patho)physiology. Cellular source and culture protocols vary between different IEO models and reliable markers for their characterization/validation are currently limited. DNA methylation has been demonstrated to play a key role in regulating gene expression and cellular function. This epigenetic mark is comparably stable and has been shown to reflect cellular identity such as tissue origin, developmental stage and age. Our genome wide DNA methylation datasets of purified human epithelium represent a unique resource, which can be used by other researchers to validate their model systems We provide the following datasets of genome-wide DNA methylation profiling by Infinium HumanMethylation450 BeadChip: Purified intestinal epithelial cells (EpCAM+) from paediatric ileum and colon, Non-epithelial mucosal cells (EpCAM-), Whole colonic mucosal biopsies, Intestinal organoid cultures from paediatric ileum and colon, Purified intestinal epithelial cells (EpCAM+) from foetal small intestine and foetal large intestine, Intestinal organoid cultures from foetal small intestine and foetal large intestine, Intestinal organoid cultures derived from induced pluripotent stem cells.<br>Note:</br><br>Some samples in this data set were previously submitted to ArrayExpress under accession number E-MTAB-3709. They're clearly marked in the âDescriptionâ field in sample annotations. </br><br>Information about batch effect during sample handling is included in the experimental variable âblockâ. Batch effect is not massive but present, so it is recommended that batch correction is carried out in data analysis.</br><br>Complementary RNA-seq data on the purified cells and organoids can be found in ArrayExpress at E-MTAB-5015 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5015/ ). </br>
2017-10-31 | E-MTAB-4957 | biostudies-arrayexpress
Project description:Human intestinal epithelial organoid models are rapidly emerging as novel experimental tools to investigate intestinal epithelial biology. A necessary aspect of organoid use is the passaging of cells and long term maintenance in culture. DNA methylation has been demonstrated to play a key role in regulating gene expression and cellular function. Here we explore the effect of culture duration, proinflammatory cytokine stimulation and differentiation on organoid DNA methylation. The experiment consists of RNA-seq of intestinal organoid cultures from paediatric ileum and colon.
2022-08-31 | E-MTAB-11548 | biostudies-arrayexpress
Project description:Human intestinal epithelial organoids (IEO) culture models are rapidly emerging as novel experimental tools to investigate fundamental aspects of intestinal epithelial (patho)physiology. Cellular source and culture protocols vary between different IEO models and reliable markers for their characterization/validation are currently limited. Here, we provide the following reference datasets of transcriptomic profiling by RNA-sequencing: Purified intestinal epithelial cells (EpCAM+) from paediatric ileum and colon, Intestinal organoid cultures from paediatric ileum and colon, Purified intestinal epithelial cells (EpCAM+) from foetal small intestine and foetal large intestine, Intestinal organoid cultures from foetal small intestine and foetal large intestine, Intestinal organoid cultures derived from induced pluripotent stem cells.<br> Complementary data from methylation profiling on the same samples have been deposited at ArrayExpress under accession number E-MTAB-4957 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-4957 ).</br>
2018-01-20 | E-MTAB-5015 | biostudies-arrayexpress
Project description:Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Differential DNA methylation predominantly occurred in regulatory enhancer regions, where known binding motifs of MRF, MEF2 and ETS proteins were identified. A transcriptional network analysis revealed modules harboring distinct ontologies, and interestingly the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus. DNA samples from vastus lateralis muscle bisopsies were included in the study. Specifically, 23 subjects performed three months of supervised endurance training. Biospies were taken at rest, before and after training. DNA methylation levels were profiled using Illumina 450K arrays.
2014-11-04 | E-GEOD-60655 | biostudies-arrayexpress
Project description:We previously reported that gut microbiota induce de novo DNA methylation of the TLR4 gene in intestinal epithelial cells. Since DNA methyltransferase (DNMT) 3 mediates the transfer of methyl groups to any gene undergoing de novo methylation, the question of how gut microbiota induce the recruitment of DNMT3 to specific genes, including TLR4, remains to be addressed. In this study, we tried to identify an adaptor molecule that recruits DNMT3b to the TLR4 gene by comparing expression of DNMT3-interacting proteins between IEC lines with hypermethylated and hypomethylated TLR4 gene.
2023-03-11 | PXD035777 | Pride
Project description:Intestinal organoids, three-dimensional cultures from intestinal stem cells, are a powerful model for studying aging, and DNA methylation is an accurate biological clock. Consequently, we hypothesized that organoid DNA methylation could serve as an aging metric and a valuable tool for in vitro aging research. Our initial study revealed significant DNA methylation changes, during organoid culture, with 27% of total CpG sites undergoing hypomethylation, and 11% gaining hypermethylation. Hypomethylation occurred predominantly in aging-associated genomic regions, including non-promoter, non-CpG island regions (e.g., transposable elements), while hypermethylation, in CpG islands, significantly (p < 0.001) correlated with aging. Comparison of aging-methylated sites with differentiation-specific CpG sites showed minimal overlap, indicating negligible association. Early-passage (P0 and P2) organoids, derived from 4- and 24-month-old mice, preserved aging-specific methylation patterns, with a correlation coefficient of 0.48 (p < 0.001) between methylation differences in old versus young primary cells. Conversely, long-term passaging revealed distinct methylation changes, specific to each organoid line. Some early passage organoids exhibited more hypomethylation, clustering with mid-passage (P10 - P13) organoids, while late-passage (P24 and P27) organoids entered a crisis stage with severe hypomethylation, growth arrest, and distant clustering. Transposable elements remained hypomethylated, compared to primary cells. Aging-related methylation sites continued to change with passage, and linear modeling predicted that organoids age at a rate of 0.46 months per week in culture. Treatment with decitabine reversed the methylation age of organoids, derived from 24-month-old mice. These findings suggest that organoids effectively model aging, with further research needed to assess culture-associated influences.
2025-06-01 | GSE295059 | GEO
Project description:Intestinal organoids, three-dimensional cultures from intestinal stem cells, are a powerful model for studying aging, and DNA methylation is an accurate biological clock. Consequently, we hypothesized that organoid DNA methylation could serve as an aging metric and a valuable tool for in vitro aging research. Our initial study revealed significant DNA methylation changes, during organoid culture, with 27% of total CpG sites undergoing hypomethylation, and 11% gaining hypermethylation. Hypomethylation occurred predominantly in aging-associated genomic regions, including non-promoter, non-CpG island regions (e.g., transposable elements), while hypermethylation, in CpG islands, significantly (p < 0.001) correlated with aging. Comparison of aging-methylated sites with differentiation-specific CpG sites showed minimal overlap, indicating negligible association. Early-passage (P0 and P2) organoids, derived from 4- and 24-month-old mice, preserved aging-specific methylation patterns, with a correlation coefficient of 0.48 (p < 0.001) between methylation differences in old versus young primary cells. Conversely, long-term passaging revealed distinct methylation changes, specific to each organoid line. Some early passage organoids exhibited more hypomethylation, clustering with mid-passage (P10 - P13) organoids, while late-passage (P24 and P27) organoids entered a crisis stage with severe hypomethylation, growth arrest, and distant clustering. Transposable elements remained hypomethylated, compared to primary cells. Aging-related methylation sites continued to change with passage, and linear modeling predicted that organoids age at a rate of 0.46 months per week in culture. Treatment with decitabine reversed the methylation age of organoids, derived from 24-month-old mice. These findings suggest that organoids effectively model aging, with further research needed to assess culture-associated influences.
2025-06-01 | GSE294963 | GEO
Project description:Epigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age-related changes in DNA methylation at the genome scale have been termed epigenetic drift, but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age-related epigenetic changes because of its substantial cell-type homogeneity and its well-known age-related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N=108) using array-based profiling of 450,000 methylation marks in various age groups. Data analysis confirmed that age-related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovers an age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome. This data set contains data from transcription profiling by array of human epidermis samples. The results of methylation profiling are provided in the ArrayExpress experiment E-MTAB-4385.
2016-03-24 | E-MTAB-4382 | biostudies-arrayexpress
Project description:Altered function of the intestinal epithelium has been considered to play a key role in CD pathogenesis, however exact mechanisms that contribute towards lifelong relapsing mucosal inflammation remain ill defined. DNA methylation (DNAm) is a key epigenetic mechanism known to determine cellular identity by regulating gene transcription with alterations increasingly being implicated in IBD pathogenesis. We generated 312 intestinal epithelial organoids (IEOs) from mucosal stem cells obtained from 168 patients diagnosed with CD, non-IBD/healthy controls and Ulcerative colitis (UC). Genome wide epigenetic profiling of IEOs and primary purified epithelium revealed highly stable, CD associated loss of DNAm in MHC-I related genes which correlated with increased gene expression. Related Single Cell Portal accession number: SCP1884 Related Gene Expression Omnibus accession numbers: GSE57945, GSE75214
2024-03-31 | E-MTAB-12841 | biostudies-arrayexpress