Reprogramming cellular identity during intestinal regeneration

The intestine is a vital organ mediating absorption of nutrients and water. Following tissue damage, the intestine mounts a remarkable regenerative response by reprogramming cellular identity to facilitate reinstatement of homeostasis. Here we review recent advances within intestinal regenerative biology and the emerging concept of fetal-like reprogramming, in which the adult intestinal epithelium transiently enters a repair-associated state reminiscent of ontologically pre-existing stages. We focus on molecular mechanisms governing reprogramming of cellular identity via epithelial-mesenchymal crosstalk, and how novel approaches in organoid technologies enable identification and characterisation of cell-autonomous repair responses within epithelial cells. Transitioning from the single-cell level to tissue scale, we discuss clonal selection following regeneration and associated pathological repurcussions such as cancer and chronic inflammatory diseases.