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| Status |
Public on Mar 12, 2024 |
| Title |
Acinar to β-like cell conversion through inhibition of focal adhesion kinase |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Insufficient functional β-cell mass causes diabetes; however, an effective cell replacement therapy for curing diabetes is currently not available. Reprogramming of acinar cells toward functional insulin-producing cells would offer an abundant and autologous source of insulin-producing cells. Our lineage tracing studies along with transcriptomic characterization demonstrate that treatment of adult mice with a small molecule that specifically inhibits kinase activity of focal adhesion kinase results in trans-differentiation of acinar cells into insulin producing β-like cells. The acinar-derived insulin-producing cells infiltrate the pre-existing endocrine islets, partially restore β-cell mass, and significantly improve glucose homeostasis in diabetic mice. Importantly, this treatment can substantially reduce the exogenous insulin requirements in streptozotocin-induced diabetic non-human primates. These findings provide evidence that inhibition of the kinase activity of focal adhesion kinase can convert acinar cells into insulin-producing cells and could offer a promising strategy for treating diabetes.
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| Overall design |
To better characterize these newly formed insulin-producing cells, we conducted single cell RNA sequencing (scRNA-seq) analysis on islets isolated from wild type mice ten days after cessation of vehicle- or FAKi treatment. Approximately 8500 cells were sequenced at 225,000 reads per cell.
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| Contributor(s) |
Esni F, Dahiya S, Rajasundaram D |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Dec 21, 2023 |
| Last update date |
Mar 12, 2024 |
| Contact name |
Dhivyaa Rajasundaram |
| E-mail(s) |
dhr11@pitt.edu
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| Organization name |
University of Pittsburgh
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| Department |
Pediatrics
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| Street address |
4401 Penn Avenue
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15224 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1055555 |
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