PLX105775

GSE109285: Pancreatic Islet-Autonomous Signals Modulate Identity Changes of Glucagon+ -Cells

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

The mechanisms restricting regeneration and maintaining cell identity upon injury are poorly characterized in higher vertebrates. Upon -cell loss, 1-2% of the glucagon-producing -cells spontaneously engage insulin production in mice. Here we explore the mechanisms of this plasticity. We show that the adaptive -cell identity changes are constrained by intra-islet Insulin- and Smoothened-mediated signaling, among others. Combining -cell loss, or insulin signaling inhibition, with Smoothened inactivation in - or -cells, stimulates insulin production in more -cells. These findings suggest that removing constitutive brake signals is crucial for neutralizing the refractoriness to adaptive cell-fate changes. It appears that cell identity maintenance is an active process mediated by repressive signals curbing an intrinsic trend of differentiated cells to change. SOURCE: Simone Gupta (gupta_simone@lilly.com) - Eli Lilly & Company