GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE109nnn/GSE109285/primaryOK2000000GenomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109285GEOGSE0falsePancreatic Islet-Autonomous Signals Modulate Identity Changes of Glucagon+ α-CellsThe mechanisms restricting regeneration and maintaining cell identity upon injury are poorly characterized in higher vertebrates. Upon β-cell loss, 1-2% of the glucagon-producing α-cells spontaneously engage insulin production in mice. Here we explore the mechanisms of this plasticity. We show that the adaptive α-cell identity changes are constrained by intra-islet Insulin- and Smoothened-mediated signaling, among others. Combining β-cell loss, or insulin signaling inhibition, with Smoothened inactivation in α- or δ-cells, stimulates insulin production in more α-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.2018/06/18GSE109285GSM2936579GSM2936557GSM2936558GSM2936559GSM2936575GSM2936553GSM2936576GSM2936554GSM2936555GSM2936577GSM2936578GSM2936556GSM2936571GSM2936572GSM2936573GSM2936552GSM2936574GSM2936570GSM2936568GSM2936569GSM2936564GSM2936565GSM2936566GSM2936567GSM2936560GSM2936561GSM2936562GSM2936563GSM2936580GSM29365811702113112SRP131035109285Mus musculus