MafB Maintains β -Cell Identity under MafA-Deficient Conditions.

The transcription factor MafB plays an essential role in β -cell differentiation during the embryonic stage in rodents. Although MafB disappears from β -cells after birth, it has been reported that MafB can be evoked in β -cells and is involved in insulin + β -cell number and islet architecture maintenance in adult mice under diabetic conditions. However, the underlying mechanism by which MafB protects β -cells remains unknown. To elucidate this, we performed RNA sequencing using an inducible diabetes model ( A0B Δpanc mice) that we previously generated. We found that the deletion of Mafb can induce β -cell dedifferentiation, characterized by the upregulation of dedifferentiation markers, Slc5a10 and Cck, as well as several β -cell-disallowed genes, and by the downregulation of mature β -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 β -cell dedifferentiation state. Collectively, our results suggest that MafB can maintain β -cell identity under certain pathological conditions in adult mice, providing novel insight into the role of MafB in β -cell identity maintenance.