MafB maintains β-cell identity under MafA-deficient condition

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 (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, and several β-cell-disallowed genes; and 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. Furtherly, the appearance of ALDH1A3+ cell and disappearance of UCN3+ cell also verify the β-cell de-differentiation state. Together, 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. Pancreatic islets mRNA profiles of 10-week-old wild type (WT), MafA-/-;MafB flox/flox (A0B2) and MafA-/-;MafB flox/flox;Pdx1-CreERTM (A0BΔpanc) mice