| First Author | Celen C | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 5 | Pages | 111581 |
| PubMed ID | 36323264 | Mgi Jnum | J:331495 |
| Mgi Id | MGI:7386621 | Doi | 10.1016/j.celrep.2022.111581 |
| Citation | Celen C, et al. (2022) Arid1a loss potentiates pancreatic beta-cell regeneration through activation of EGF signaling. Cell Rep 41(5):111581 |
| abstractText | The dynamic regulation of beta-cell abundance is poorly understood. Since chromatin remodeling plays critical roles in liver regeneration, these mechanisms could be generally important for regeneration in other tissues. Here, we show that the ARID1A mammalian SWI/SNF complex subunit is a critical regulator of beta-cell regeneration. Arid1a is highly expressed in quiescent beta-cells but is physiologically suppressed when beta-cells proliferate during pregnancy or after pancreas resection. Whole-body Arid1a knockout mice are protected against streptozotocin-induced diabetes. Cell-type and temporally specific genetic dissection show that beta-cell-specific Arid1a deletion can potentiate beta-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets reveal increased neuregulin-ERBB-NR4A signaling. Chemical inhibition of ERBB or NR4A1 blocks increased regeneration associated with Arid1a loss. Mammalian SWI/SNF (mSWI/SNF) complex activity is a barrier to beta-cell regeneration in physiologic and disease states. |
