Expression data from PolyIC treated EndoC-ßH1 cells

Type 1 diabetes (T1D) is a chronic disease characterized by an autoimmune-mediated destruction of insulin-producing pancreatic β cells. Environmental factors such as viruses play an important role in the onset of T1D and interact with predisposing genes. Recent data suggest that viral infection of human islets leads to a decrease in insulin production rather than β cell death, suggesting loss of β cell identity. We undertook this study to examine whether viral infection could induce human ß cell dedifferentiation. Using the functional human β cell line EndoC-βH1, we demonstrate that polyinosinic-polycitidilic acid (PolyI:C), a synthetic double-stranded RNA that mimics a by-product of viral replication induces a decrease in β cell-specific gene expression. In parallel to this loss, the expression of progenitor-like genes such as SOX9 was activated following PolyI:C treatment or enteroviral infection. SOX9 was induced by the NF-kB pathway and also in a paracrine non-cell autonomous fashion through the secretion of IFNA. Finally, we identified new SOX9 targets in human β cells as new markers of dedifferentiation in T1D. These findings reveal that inflammatory signaling has clear implications in human β cell dedifferentiation. EndoC-ßH1 cells were treated with PolyIC for RNA extraction and hybridization on Affymetrix microarrays