Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon α-cells.

Cigliola V, Ghila L, Thorel F, van Gurp L, Baronnier D, Oropeza D, Gupta S, Miyatsuka T, Kaneto H, Magnuson MA, Osipovich AB, Sander M, Wright CEV, Thomas MK, Furuyama K, Chera S, Herrera PL
Nat Cell Biol. 2018 20 (11): 1267-1277

PMID: 30361701 · PMCID: PMC6215453 · DOI:10.1038/s41556-018-0216-y

The mechanisms that restrict regeneration and maintain cell identity following injury are poorly characterized in higher vertebrates. Following β-cell loss, 1-2% of the glucagon-producing α-cells spontaneously engage in insulin production in mice. Here we explore the mechanisms inhibiting α-cell plasticity. We show that adaptive α-cell identity changes are constrained by intra-islet insulin- and Smoothened-mediated signalling, among others. The combination of β-cell loss or insulin-signalling inhibition, with Smoothened inactivation in α- or δ-cells, stimulates insulin production in more α-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.

MeSH Terms (16)

Animals Cell Differentiation Cell Plasticity Cell Proliferation Female Glucagon-Secreting Cells Insulin Insulin-Secreting Cells Islets of Langerhans Male Mice, Inbred C57BL Mice, Knockout Mice, SCID Mice, Transgenic Signal Transduction Smoothened Receptor

Connections (5)

This publication is referenced by other Labnodes entities: