Dysfunction of intestinal epithelial cells is often associated with severe gut pathologies, such as inflammatory bowel disease (IBD). Although transcriptional signatures of intestinal cells have been identified, an integrated network analysis of specific cell types which identifies key regulators and disease relevance has been lacking. Here, we profiled the expression of mRNAs, microRNAs and long non-coding RNAs from mouse derived 3D intestinal organoids whose differentiation was directed towards Paneth cells or goblet cells. We generated regulatory networks specific to these cell types by integrating expression data into networks of transcriptional and post-transcriptional regulatory interactions. Analysis of the networks uncovered potential cell-type specific master regulators and highlighted possible regulatory rewiring between the cell types. Investigation of regulators identified links to cellular phenotypes associated with IBD. Application of our workflow can be used to disentangle multifactorial mechanisms of IBD and to propose regulators whose pharmacological targeting could be advantageous in treating Crohn’s disease.
