Projects per year
Abstract
Type 1 diabetes (T1D) is an autoimmune disease that selectively destroys insulin-producing β-cells in the pancreas. An unmet need in diabetes management, current therapy is focussed on transplantation. While the reprogramming of progenitor cells into functional insulin-producing β-cells has also been proposed this remains controversial and poorly understood. The challenge is determining why default transcriptional suppression is refractory to exocrine reactivation. After the death of a 13-year-old girl with established insulin-dependent T1D, pancreatic cells were harvested in an effort to restore and understand exocrine competence. The pancreas showed classic silencing of β-cell progenitor genes with barely detectable insulin (Ins) transcript. GSK126, a highly selective inhibitor of EZH2 methyltransferase activity influenced H3K27me3 chromatin content and transcriptional control resulting in the expression of core β-cell markers and ductal progenitor genes. GSK126 also reinstated Ins gene expression despite absolute β-cell destruction. These studies show the refractory nature of chromatin characterises exocrine suppression influencing β-cell plasticity. Additional regeneration studies are warranted to determine if the approach of this n-of-1 study generalises to a broader T1D population.
Original language | English |
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Article number | 248 |
Number of pages | 9 |
Journal | Signal Transduction and Targeted Therapy |
Volume | 7 |
Issue number | 1 |
DOIs | |
Publication status | Published - 22 Jul 2022 |
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Cytosine methylation predicts diabetic nephropathy progression
El-Osta, S., Groop, P., Khurana, I. & Maxwell, S. S.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/21 → 31/12/23
Project: Research
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New models of gene regulation in diabetic complications
El-Osta, S. & Khurana, I.
1/01/19 → 31/12/23
Project: Research