Transcriptional and functional characterization of human intestinal organoid and monolayer models for IBD-therapeutic development

Intestinal organoids have the potential to replicate cellular diversity and functional biology of the human gut, suggesting their application in Inflammatory Bowel Disease (IBD) research. Insufficient characterization at the molecular, cellular, and functional level has remained a barrier to their use in drug discovery. We profile intestinal organoids and Transwell-monolayers derived from ileum and colon tissue of control and IBD subjects. Organoids and monolayers respond to optimized differentiation media with consistent expression and maturation patterns, including signatures of epithelial cell types found in the human gut. Both ileum- and colon-derived monolayers show acute sensitivity to cytokines with applicability for modeling epithelial barrier damage. Instestinal organoid and monolayer cultures derived from healthy and IBD colon and ileum where grown in three different differentiation media