APA
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Lietzke, A., Walker, E. M., Bealer, E. J., Crumley, K., King, J. L., Stendahl, A. M., … Soleimanpour, S. (2025). Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells. Nature Communications.
Chicago/Turabian
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Lietzke, Anne, Emily M. Walker, Elizabeth J. Bealer, Kelly Crumley, Jessica L King, Ava M. Stendahl, Jie Zhu, et al. “Limitations in PPARα-Dependent Mitochondrial Programming Restrain the Differentiation of Human Stem Cell-Derived β Cells.” Nature Communications (2025).
MLA
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Lietzke, Anne, et al. “Limitations in PPARα-Dependent Mitochondrial Programming Restrain the Differentiation of Human Stem Cell-Derived β Cells.” Nature Communications, 2025.
BibTeX Click to copy
@article{anne2025a,
title = {Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells},
year = {2025},
journal = {Nature Communications},
author = {Lietzke, Anne and Walker, Emily M. and Bealer, Elizabeth J. and Crumley, Kelly and King, Jessica L and Stendahl, Ava M. and Zhu, Jie and Pearson, Gemma L. and Levi-D'Ancona, Elena and Henry-Kanarek, Belle A. and Davidson, Rebecca K. and Li, Jin and Reck, Emma C. and Wu, Yifei and Arnipalli, M. and Pham, John-Paul A and Mundada, Lakshmi and Sidarala, Vaibhav and Herron, Todd J. and Coronel, Maria M. and Pennathur, Subramaniam and Madsen, J. G. and Shea, Lonnie D. and Soleimanpour, S.}
}
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 alterations in mitochondrial mass, structure, or genome integrity. In contrast, SC-islets show limited expression of targets of PPARα, which regulate mitochondrial programming, yet whose functions in β cell differentiation are unknown. Importantly, treatment with WY14643, a potent PPARα agonist, induces expression of mitochondrial targets, improves insulin secretion, and increases the formation of SC-β cells both in vitro and following transplantation. Thus, PPARα-dependent mitochondrial programming promotes the differentiation of SC-β cells and may be a promising target to improve β cell replacement efforts for T1D. Here they show that PPARα-dependent mitochondrial programming promotes the differentiation of pluripotent stem cell-derived β cells. Targeting mitochondria has the potential to improve β cell replacement efforts for the treatment of type 1 diabetes.