Colitis memory: Epigenetic changes in colon stem cells drive tumor growth
In a mouse model, repeated colitis leaves a durable, cell-intrinsic epigenetic memory in colonic stem cells, marked by progressive AP-1 activity and lasting chromatin accessibility changes for over 100 days after recovery. This memory is clonally inherited and primes stem cells for enhanced AP-1–driven gene expression after oncogenic mutation, accelerating early tumor growth. AP-1 inhibition slows tumor size but does not erase memory; the work also reveals cooperative AP-1/FOX binding and shows parallels in human organoids, suggesting diagnostic and therapeutic routes to reduce cancer risk in chronic inflammatory disease.