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

Abstract

ABSTRACTThe 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 (A0BΔpanc 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.