Modeling the effect of prolonged ethanol exposure on global gene expression and chromatin accessibility in normal 3D colon organoids
Autoři:
Matthew Devall aff001; Lucas T. Jennelle aff001; Jennifer Bryant aff001; Stephanie Bien aff002; Ulrike Peters aff002; Steven Powell aff003; Graham Casey aff001
Působiště autorů:
Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States of America
aff001; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
aff002; Digestive Health Center, Gastroenterology and Heaptology, University of Virginia, Charlottesville, Virginia, United States of America
aff003
Vyšlo v časopise:
PLoS ONE 15(1)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0227116
Souhrn
In this study we aimed to explore the potential biological effect of ethanol exposure on healthy colon epithelial cells using normal human colon 3D organoid “mini-gut” cultures. In numerous published studies ethanol use has been shown to be an environmental risk factor for colorectal cancer (CRC) development; however, the influence of ethanol exposure on normal colon epithelial cell biology remains poorly understood. We investigated the potential molecular effects of ethanol exposure in normal colon 3D organoids in a small pilot study (n = 3) using RNA-seq and ATAC-seq. We identify 1965 differentially expressed genes and 2217 differentially accessible regions of chromatin in response to ethanol treatment. Further, by cross-referencing our results with previously published analysis in colorectal cancer cell lines, we have not only validated a number of reported differentially expressed genes, but also identified several novel candidates for future investigation. In summary, our data highlights the potential importance for the use of normal colon 3D organoid models as a novel tool for the investigation of the relationship between the effects of environmental risk factors associated with colorectal cancer and the molecular mechanisms through which they confer this risk.
Klíčová slova:
Colon – Colorectal cancer – Ethanol – Gene expression – Genomic libraries – Chromatin – Organoids – RNA isolation
Zdroje
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