Summary of project PR002703
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002703. The data can be accessed directly via it's Project DOI: 10.21228/M88851 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002703 |
| Project DOI: | doi: 10.21228/M88851 |
| Project Title: | Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells |
| Project Summary: | 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 observed 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 PPAR⍺, which regulate mitochondrial programming, yet whose functions in β cell differentiation are unknown. Importantly, treatment with WY14643, a potent PPAR⍺ agonist, induced expression of mitochondrial targets, improved insulin secretion, and increased the formation of SC-β cells both in vitro and following transplantation. Thus, PPAR⍺-dependent mitochondrial programming promotes the differentiation of SC-β cells and may be a promising target to improve β cell replacement efforts for T1D. |
| Institute: | University of Michigan |
| Department: | Division of Metabolism, Endocrinology and Diabetes and Department of Internal Medicine |
| Laboratory: | Scott A. Soleimanpour |
| Last Name: | Arnipalli |
| First Name: | Manikanta |
| Address: | 3815-301B Green Brier apt, Ann Arbor, michigan, 48105, USA |
| Email: | manikana@umich.edu |
| Phone: | 734-272-8779 |
Summary of all studies in project PR002703
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004277 | Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells | Homo sapiens | University of Michigan | MS | 2025-10-31 | 1 | 68 | Uploaded data (98G)* |
| ST004286 | Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells - Study 2 | Homo sapiens | University of Michigan | MS | 2025-11-03 | 1 | 29 | Uploaded data (107.4M)* |
