Extensive jejunal injury is repaired by migration and transdifferentiation of ileal enterocytes in zebrafish

A major cause of intestinal failure (IF) is intestinal epithelium necrosis and massive loss of enterocytes, especially in the jejunum, the major intestinal segment in charge of nutrient absorption. However, mechanisms underlying jejunal epithelial regeneration after extensive loss of enterocytes remain elusive. Here, we apply a genetic ablation system to induce extensive damage to jejunal enterocytes in zebrafish, mimicking the jejunal epithelium necrosis that causes IF. In response to injury, proliferation and filopodia/lamellipodia drive anterior migration of the ileal enterocytes into the injured jejunum. The migrated fabp6+ ileal enterocytes transdifferentiate into fabp2+ jejunal enterocytes to fulfill the regeneration, consisting of dedifferentiation to precursor status followed by redifferentiation. The dedifferentiation is activated by the IL1b-NFkB axis, whose agonist promotes regeneration. Extensive jejunal epithelial damage is repaired by the migration and transdifferentiation of ileal enterocytes, revealing an intersegmental migration mechanism of intestinal regeneration and providing potential therapeutic targets for IF caused by jejunal epithelium necrosis.

Automated summary

A major cause of intestinal failure is intestinal epithelium necrosis and loss of enterocytes, particularly in the jejunum. The mechanisms behind jejunal epithelial regeneration after extensive loss of enterocytes are unknown. In this study, zebrafish were used to induce extensive damage to jejunal enterocytes, mimicking the necrosis observed in intestinal failure. It was found that ileal enterocytes migrate and transdifferentiate into jejunal enterocytes to fulfill the regeneration process. The IL1b-NFkB axis and its agonist play a role in activating dedifferentiation and promoting regeneration. This research provides insights into the intersegmental migration mechanism of intestinal regeneration and potential therapeutic targets for intestinal failure caused by jejunal epithelium necrosis.