MafB Maintains beta-Cell Identity under MafA-Deficient Conditions

The transcription factor MafB plays an essential role in beta-cell differentiation during the embryonic stage in rodents. Although MafB disappears from beta-cells after birth, it has been reported that MafB can be evoked in beta-cells and is involved in insulin(+) beta-cell number and islet architecture maintenance in adult mice under diabetic conditions. However, the underlying mechanism by which MafB protects beta-cells remains unknown. To elucidate this, we performed RNA sequencing using an inducible diabetes model (A0B(Delta panc) mice) that we previously generated. We found that the deletion of Mafb can induce beta-cell dedifferentiation, characterized by the upregulation of dedifferentiation markers, Slc5a10 and Cck, as well as several beta-cell-disallowed genes, and by the downregulation of mature beta-cell markers, Slc2a2 and Ucn3. However, there is no re-expression of well-known progenitor cell markers, Foxo1 and Neurog3. Further, the appearance of ALDH1A3(+) cells and the disappearance of UCN3(+) cells also verify the beta-cell dedifferentiation state. Collectively, our results suggest that MafB can maintain beta-cell identity under certain pathological conditions in adult mice, providing novel insight into the role of MafB in beta-cell identity maintenance.