Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells.

ABSTRACT: Pluripotent stem cell (SC)-derived islets offer hope as a renewable source for β cell replacement for type 1 diabetes (T1D), yet functional and metabolic immaturity may limit their long-term therapeutic potential. Here, we show that limitations in mitochondrial transcriptional programming impede the formation of SC-derived β (SC-β) cells. Utilizing transcriptomic profiling, assessments of chromatin accessibility, mitochondrial phenotyping, and lipidomics analyses, we observe that SC-β cells exhibit reduced oxidative and mitochondrial fatty acid metabolism compared to primary human islets that are related to limitations in key mitochondrial transcriptional networks. Surprisingly, we find that reductions in glucose-stimulated mitochondrial respiration in SC-islets were not associated with al

SUBMITTER: Lietzke AC 

PROVIDER: S-EPMC12695878 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature