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Cell-intrinsic aryl hydrocarbon receptor signalling is required for the resolution of injury-induced colonic stem cells
- Publication Year :
- 2022
- Publisher :
- The Francis Crick Institute, 2022.
-
Abstract
- The aryl hydrocarbon receptor (AHR) is an environmental sensor that integrates microbial and dietary cues to influence physiological processes within the intestinal microenvironment, protecting against colitis and colitis-associated colorectal cancer development. Rapid tissue regeneration upon injury is important for the reinstatement of barrier integrity and its dysregulation promotes malignant transformation. Here we show that AHR is important for the termination of the regenerative response and the reacquisition of mature epithelial cell identity post injury in vivo and in organoid cultures in vitro. Using an integrative multi-omics approach in colon organoids, we show that AHR is required for timely termination of the regenerative response through direct regulation of transcription factors involved in epithelial cell differentiation as well as restriction of chromatin accessibility to regeneration-associated Yap/Tead transcriptional targets. Safeguarding a regulated regenerative response places AHR at a pivotal position in the delicate balance between controlled regeneration and malignant transformation.
- Subjects :
- Model organisms
Chemical Biology & High Throughput
Multidisciplinary
Colon
Stem Cells
FOS: Clinical medicine
Genome Integrity & Repair
Immunology
Neurosciences
General Physics and Astronomy
Gene Expression
General Chemistry
Tumour Biology
General Biochemistry, Genetics and Molecular Biology
Signalling & Oncogenes
Receptors, Aryl Hydrocarbon
Synthetic Biology
Intestinal Mucosa
Genetics & Genomics
Signal Transduction
Developmental Biology
Computational & Systems Biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ee9d0c2fadf5822c8ef8a768a2bad770
- Full Text :
- https://doi.org/10.25418/crick.19575367