| First Author | Cigliola V | Year | 2018 |
| Journal | Nat Cell Biol | Volume | 20 |
| Issue | 11 | Pages | 1267-1277 |
| PubMed ID | 30361701 | Mgi Jnum | J:268101 |
| Mgi Id | MGI:6270701 | Doi | 10.1038/s41556-018-0216-y |
| Citation | Cigliola V, et al. (2018) Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon(+) alpha-cells. Nat Cell Biol 20(11):1267-1277 |
| abstractText | The mechanisms that restrict regeneration and maintain cell identity following injury are poorly characterized in higher vertebrates. Following beta-cell loss, 1-2% of the glucagon-producing alpha-cells spontaneously engage in insulin production in mice. Here we explore the mechanisms inhibiting alpha-cell plasticity. We show that adaptive alpha-cell identity changes are constrained by intra-islet insulin- and Smoothened-mediated signalling, among others. The combination of beta-cell loss or insulin-signalling inhibition, with Smoothened inactivation in alpha- or delta-cells, stimulates insulin production in more alpha-cells. These findings suggest that the removal of constitutive 'brake signals' is crucial to neutralize the refractoriness to adaptive cell-fate changes. It appears that the maintenance of cell identity is an active process mediated by repressive signals, which are released by neighbouring cells and curb an intrinsic trend of differentiated cells to change. |
