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Distinct Molecular Responses of Human Intestinal Organoids to Proton and Photon Radiation

ABSTRACT: Radiation exposure causes damage to tissues with high numbers of rapidly dividing cells such as the intestine. Mouse models have been widely used to understand the effects of radiation injury, repair following exposure, and to develop and test potential therapies for radiation-induced damage. However, although the mouse intestine shares physiological and molecular similarities with human intestine, translation and validation of findings in mouse radiation models to the human intestine have been limited by the lack of models. The development of ex vivo human intestinal organoids provides a new model in which the effects of radiation on the human intestinal epithelium can be examined and compared to in vivo animal models. Using human small intestinal jejunal organoids, multi-omic profiles were analyzed using bioinformatic pipelines to explore the response to a dose of proton and photon radiation exposure which may be encountered during a radiotherapy treatment or over time in high background radiation environments. Transcriptional signatures following radiation exposure were indicative of reprogramming of cells to a more primitive state that has been associated with regeneration and repair. Integrative analyses of transcriptomic and metabolomic datasets revealed enrichment of amino acid synthesis and metabolism pathways. Human intestinal organoids can complement and validate findings from traditional animal models and are emerging as a powerful tool to study responses to radiation exposure.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297090 | GEO | 2025/10/28

REPOSITORIES: GEO

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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. Note: 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. 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. 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/ ).

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Distinct Molecular Responses of Human Intestinal Organoids to Proton and Photon Radiation

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