Enhancing our understanding of intercellular communication to achieve programmable regeneration

PROJECT SUMMARY The capacity for tissues and organs to heal and regenerate in response to injury has set the stage for regenerative medicine, making numerous procedures possible, including the generation of in vitro organ culture and transplantation. While this technology holds great promise for the future of medicine, the full translation of regenerative biology into clinical settings has been limited by a lack of mechanistic understanding underlying how different regenerative outcomes are achieved. Specifically, the endogenous and exogenous signals that determine in vitro cellular organization during regeneration and ultimately, coordinate successful versus failed transplantation and de novo coordination with host tissues remains elusive. To fill this knowledge gap, this proposal uses a model plant system that exhibits exceptional regenerative capacities to advance our understanding of how intercellular communication coordinates with endogenous cellular signaling to direct specific regenerative trajectories. This system will be used to gain mechanistic insight into the intercellular interactions that shape diverse regenerative potentials, by (1) mapping the cellular and developmental trajectories that lead to different regenerative outcomes, (2) exploring the role of intercellular signaling in shaping these regenerative paths, and (3) testing the extent to which gene regulatory circuits can be perturbed to break and rebuild intercellular coordination during regeneration. In addition, the potential for programmable regenerative engineering to produce predictive regenerative outcomes and rescue tissue rejection during incompatible grafting will be tested through the quantitative design of cellular implants. Taken together, this proposed research will not only provide basic insights into regenerative cell biology, but also open up to the development of truly synthetic environmental conditions that can robustly recreate targeted regenerative outcomes.