TY - JOUR T1 - Functional, metabolic and transcriptional maturation of stem cell derived beta cells JF - bioRxiv DO - 10.1101/2021.03.31.437748 SP - 2021.03.31.437748 AU - Diego Balboa AU - Tom Barsby AU - Väinö Lithovius AU - Jonna Saarimäki-Vire AU - Muhmmad Omar-Hmeadi AU - Oleg Dyachok AU - Hossam Montaser AU - Per-Eric Lund AU - Mingyu Yang AU - Hazem Ibrahim AU - Anna Näätänen AU - Vikash Chandra AU - Helena Vihinen AU - Eija Jokitalo AU - Jouni Kvist AU - Jarkko Ustinov AU - Anni I. Nieminen AU - Emilia Kuuluvainen AU - Ville Hietakangas AU - Pekka Katajisto AU - Joey Lau AU - Per-Ola Carlsson AU - Sebastian Barg AU - Anders Tengholm AU - Timo Otonkoski Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/01/2021.03.31.437748.abstract N2 - Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in stem cell-derived islet (SC-islet) generation, detailed characterization of their functional properties has not been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and comprehensively benchmarked them against primary adult islets. Biphasic glucose stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and increased alpha cells. Electrophysiology and exocytosis of SC-islets were comparable to adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of murine engraftment revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.Competing Interest StatementThe authors have declared no competing interest. ER -