Quantitative Analysis Of Mitotic Activity And Telomere Length Reveals The Existence Of Progenitor Cells Within Murine Pancreatic Islets

Maintaining adequate islet beta cell mass in the adult pancreas is central to achieving euglycemia. However, the mechanisms of beta cell dynamics in postnatal animals are still poorly defined. In this study, we provided evidences that cell-cycle activity and aging, determined by Ki67 expression/BrdU incorporation and telomere length respectively, were two markers which could be used to characterize the developmental stages of islets. The results showed that both parameters were not displayed homogeneously by individual islets from the pancreas, including a up to 32-fold difference in Ki67 transcripts and a 3-fold variation in the percentage of BrdU positive cells from mice of 12 day old or 4 month old. Similarly, the telomere length in single islets differed by 1.5-3 folds. More importantly, Ki67 transcript levels were significantly correlated with telomere lengths measured in single islets. Furthermore, this heterogeneity was found to represent differential existence of islet progenitor cells which were revealed by label retaining measurement and single cell analysis. Thus, islet cell mass in the adult pancreas was maintained by the expansion of progenitor cells and their immediate progenies rather than by the replication of fully differentiated beta cells.