Key Developmental Regulators Suggest Multiple Origins of Pancreatic Beta Cell Regeneration

Abstract

Extensive efforts have been done to try to restore the lost β cell mass for the cure of diabetes. Animal models have been established to provide evidences of cellular origins and contextual regulators of β cell regeneration. Here, we used a zebrafish β cell ablation and regeneration model to investigate β cell neogenesis in the first few days after a near-total β cell loss. Regeneration of β cells first occurred within 7 h post-treatment. Developmental regulators such as neurod, pdx1, mnx1, and nkx2.2a were active in the regenerating β cells, while at the same time suggesting different subpopulations of regenerative cellular origins. Using Cre/loxP-based lineage tracing, we showed that intrapancreatic ductal cells resisted to give rise to regenerating β cells. Given that transdifferentiation of α cell and δ cell can regenerate β cell, here we have provided further molecular evidence highly suggesting that the regenerating β cells originate from multiple cellular origins.