Virgin Beta Cells at the Neogenic Niche Proliferate Normally and Mature Slowly.

Proliferation of pancreatic beta cells has long been known to reach its peak in the neonatal stages and decline during adulthood. However, beta cell proliferation has been studied under the assumption that all beta cells constitute a single, homogenous population. It is unknown whether a subpopulation of beta cells retains the capacity to proliferate at a higher rate and thus contributes disproportionately to the maintenance of mature beta cell mass in adults. We therefore assessed the proliferative capacity and turnover potential of virgin beta cells, a novel population of immature beta cells found at the islet periphery. We demonstrate that virgin beta cells can proliferate but do so at rates similar to those of mature beta cells from the same islet under normal and challenged conditions. Virgin beta cell proliferation rates also conform to the age-dependent decline previously reported for beta cells at large. We further show that virgin beta cells represent a long-lived, stable subpopulation of beta cells with low turnover into mature beta cells under healthy conditions. Our observations indicate that virgin beta cells at the islet periphery can divide but do not contribute disproportionately to the maintenance of adult beta cell mass.