Conversion of α-Cells to β-Cells in the Postpartum Mouse Pancreas Involves Lgr5 Progeny
| Autor: | Angela Criscimanna, Nada Mohamed, George K. Gittes, Uylissa A. Rodriguez, Jing Hu, Farzad Esni, Krishna Prasadan, Christina P. Martins, Mairobys Socorro |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Population Apoptosis Endogeny Biology Receptors G-Protein-Coupled Mice Insulin-Secreting Cells Internal Medicine medicine Animals Compartment (development) Cell Lineage Involution (medicine) Progenitor cell education Pancreas education.field_of_study Stem Cells Postpartum Period LGR5 Cell Differentiation Cell biology Mice Inbred C57BL medicine.anatomical_structure Islet Studies Glucagon-Secreting Cells Female Adult stem cell |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db20-1059 |
| Popis: | 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 patients with diabetes, 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 lineage conversion of α- to β-cells specifically after parturition. The contribution of Lgr5 progeny to the β-cell compartment through an α-cell intermediate phase early after pregnancy appears to be part of a novel mechanism that would counterbalance against excessive β-cell mass reduction during β-cell involution. |
| Databáze: | OpenAIRE |
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