Isolation of live human δ cells for genetic and functional analysis

Abstract

Investigations of human pancreatic islets have been empowered by strategies to isolate and study live islet cell subsets, like β cells and α cells. To advance experimentation with human islet δ cells, which remain relatively understudied, we generated combinatorial cell sorting approaches to separate human δ cells from β cells, yielding highly-enriched human δ cells. We used molecular analysis, immunohistology, and electroporation-based targeting to demonstrate the quality of δ cell purification. We also demonstrated the feasibility of prospectively studying human δ cell function in pseudoislet organoids. Innovations detailed here should promote discovery of genetic, signaling and physiological mechanisms governing δ cell function and roles in human islets.