Isolation of Live Human δ Cells for Genetic and Functional Analysis

Elsevier

Available online 11 June 2025, 102188

Molecular MetabolismAuthor links open overlay panel, , , , Highlights•

Created a novel flow sorting strategy to purify live human islet δ cells

Isolated live human δ cells suitable for gene regulation assays

Selectively transduced live human δ cells by electroporation

δ cell-depleted pseudoislets enabled study of human intra-islet cell interactions

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.

Key Words

Human islet: δ cells

β cells

α cells

pseudoislet

pancreas

diabetes

© 2025 Published by Elsevier GmbH.

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