Transdifferentiation of pancreatic duct cells to β-cells in absence of the transcription factor HNF6

(eng) A promising way to cure diabetes is to implant in vitro produced β-cells, or to induce β-cell regeneration in vivo. Multiple attempts have been made to coax different cell types into β-cells. One of these cell types is the pancreatic duct cell, but its potential as a β-cell precursor remains unclear. In this work we examine the plasticity of duct cells in mice deficient for Hepatocyte Nuclear Factor 6 (HNF6), a transcriptional regulator of pancreatic cell differentiation. In hnf6-/- mice, the number of β-cells is reduced at birth, yet it subsequently undergoes a partial recovery. We show in these mice that a postnatalβ-cell neogenesis occurs. Neogenesis neither results from a higher proliferation rate of mature β-cells nor from delayed differentiation of β-cell precursors. The presence of transition cells that co-express insulin and duct markers, as well as genetic lineage tracing, indicate that duct cells transdifferentiate postnatally to β-cells in hnf6-/- mice. Therefore, our results provide evidence that in the absence of the transcription factor HNF6, duct cells have the potential to generate β-cells. This suggests new strategies for the production of β-cells from duct cells.