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Ethanol exposure drives colon location specific cell composition changes in a normal colon crypt 3D organoid model
Matthew Devall1, Sarah J Plummer1, Jennifer Bryant1
1Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Scientific Reports
|January 12, 2021
Summary
Ethanol exposure alters gene expression and cell composition in healthy colon organoids, increasing transit amplifying cells, particularly in the left colon. This suggests a mechanism for alcohol-induced colon cancer risk.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cancer Research
Background:
- Alcohol consumption is a known risk factor for colon cancer.
- The precise molecular mechanisms by which alcohol affects normal colon crypt cells are not fully understood.
Purpose of the Study:
- To investigate the transcriptomic and cellular responses of healthy colon organoids to ethanol exposure.
- To explore potential differences in response based on colon location.
Main Methods:
- RNA-sequencing was used to analyze gene expression changes in 34 healthy colon organoid lines after ethanol treatment.
- Single-cell RNA-sequencing data and deconvolution methods were employed to infer cell-type-specific alterations.
- Differential gene expression analysis and cell proportion estimation were performed.
Main Results:
- Ethanol exposure resulted in 2,162 differentially expressed genes.
- Organoids from the left colon showed a greater number of differentially expressed genes compared to the right colon.
- Ethanol increased transit amplifying cells and decreased differentiated cells, with a more pronounced effect in left colon organoids.
Conclusions:
- Ethanol exposure alters gene expression and cell composition in colon organoids, impacting the balance of cell proliferation and differentiation.
- These changes, particularly the increase in transit amplifying cells in the lower crypt, may contribute to the increased risk of colon cancer associated with alcohol consumption.
