Inflammatory Bowel Diseases (IBDs) are typified by bouts of inflammation-induced epithelial damage and repair. By take cues from their microenvironment or “niche”, intestinal stem cells (ISCs) direct these fluctuating pathological and reparative states in IBD. Yet, we do not understand which cells comprise the inflamed ISC niche and how they switch on programs of repair. To track evolving ISC niches, we are proposing the development of a new cutting-edge Niche-labeling system. Our ultimate goal is to understand how ISC niches change over the course of disease and leverage this information to reprogram an “inflammatory ISC niche” into a “regenerative ISC niche” and achieve lasting remission in IBD.