Photoresponsive materials to study matricellular signaling dynamics during crypt formation and fission

The small intestine's epithelial layer is maintained by intestinal stem cells (ISCs) and crypt fission, a process where a single crypt divides to form a new daughter crypt, essential for intestinal health and regeneration. Despite its importance in injury repair and its mis-regulation in diseases like inflammatory bowel disease, the mechanisms of crypt fission initiation, progression, and regulation are poorly understood. The proposed research will utilize innovative photoresponsive hydrogels for culturing intestinal organoids to create a robust and predictable in vitro model of crypt fission events. This reductionist approach will allow precise tuning of the ISC niche properties to understand how epithelial cells and ECM signaling contribute to crypt formation and fission. Hypotheses will be tested regarding the role of crypt cells and matricellular signaling on organoid symmetry breaking, crypt formation, crypt fission, and potential compensatory cellular responses to local tissue damage.