Alpha to Beta Cell Conversion in the Postpartum Mouse Pancreas involves Lgr5 Progeny

In contrast to the skin and the gut, where somatic stem cells and their niche are well characterized, a definitive pancreatic multipotent cell population in the adult pancreas has yet to be revealed. Of particular interest is whether such cells may be endogenous in diabetic patients, and if so, can they be used for therapeutic purposes. In the current study, we used two separate reporter lines to target Cre-recombinase expression to the Lgr5 or glucagon expressing cells in the pancreas. We provide evidence for the existence of a population of cells within and in the proximity of the ducts that transiently express the stem cell marker Lgr5 during late gestational stages. Careful timing of tamoxifen treatment in Lgr5^{EGFP-IRES-CreERT2};R26^Tomato mice allowed us to show that these Lgr5-expressing progenitor cells can differentiate into α-cells during pregnancy. Furthermore, we report on a spontaneous α-to β-cell lineage conversion specifically after parturition. The contribution of Lgr5-progeny to the β-cell compartment through an α-cell intermediate phase early on after pregnancy appears to be part of a novel mechanism that would counterbalance against excessive β-cell mass reduction during β-cell involution.