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

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posted on 27.04.2021, 16:33 by Uylissa A. Rodriguez, Mairobys Socorro, Angela Criscimanna, Christina P. Martins, Nada Mohamed, Jing Hu, Krishna Prasadan, George K. Gittes, Farzad Esni
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 Lgr5EGFP-IRES-CreERT2;R26Tomato 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.

Funding

Supported by NIH/NIDDK grants R01DK101413 (to F.E.) and R01DK120698 (to GKG and F.E.), NCI grant CA236965 (to J.H and F.E), RAC (to F.E) and The Children’s Hospital of Pittsburgh of UPMC (to F.E.).

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