Physically interacting beta-delta pairs in the regenerating pancreas revealed by single-cell sequencing

We report that delta cells are Sox9 descendants that expand at the periphery of the regenerating islets following partial pancreatectomy. We further characterize regeneration-driven heterogeneity of beta cells at a single-cell resolution, demonstrating sub-populations of ER-stressed, proliferating and highly-functioning beta-cells. We further systematically map sub populations of beta-cells that are paired with other endocrine cell types. Our analysis suggests that the particular cluster of beta-cells that pair with delta-cells benefits from stress protection, implying that the interaction between beta and delta-cells safeguards against regeneration-associated challenges. Single-cell RNA seq on dissociated isolated islets, 4 weeks following partial pancreatectomy. Data of 2300 cells collected from 6 pancreata analyzed by MetaCell