It has been well documented that there are abundant endocrine progenitor cells in the neonatal pancreas. However, little is known of their relative proportions or even their phenotypes. The aim of this study was to examine the normal distribution and characteristics of putative endocrine precursor cells, identified by c-Kit or nestin expression, within the prenatal and postnatal rat pancreas during islet cell development. Here, we provide evidence of the existence of a subset of ductal, islet, and acinar cells with an immature morphology and high proliferative capacity that expressed c-Kit or nestin. The proportion of islet cells expressing c-Kit or nestin was highest at embryonic day 18 (25 +/- 4% and 28 +/- 6%) and decreased significantly by postnatal day 28 (P < 0.01), 1.3 +/- 0.2% and 5.7 +/- 1%, respectively. The expression of nestin mRNA decreased throughout development, while c-Kit mRNA expression was found to slightly increase in the developing pancreas. Coexpression patterns indicated that c-Kit and nestin form two distinct cell populations in the postnatal pancreas, and infrequently coexpress with other pancreatic cell-specific markers. Furthermore, decreased c-Kit and nestin expression in the islets in postnatal life correlated with an increase in cells immunopositive for Pdx-1 compared with birth (36 +/- 5% vs. 60 +/- 3%, P < 0.01), which accompanied a doubling in the proportion of Glut-2-positive cells (39.4 +/- 4% vs. 68.8 +/- 3%, P < 0.01), both of which are mature beta-cell markers. Taken together, these findings suggest that c-Kit- and nestin-expressing cells represent endocrine precursor cells that undergo marked changes in population dynamics during the transition from prenatal to postnatal pancreatic development in the rat. Characterization of the phenotype, relative abundance and location of these cells within the developing pancreas is an important step toward creating a strategy for isolating stem cell populations and modeling islet cell differentiation in vitro.
Copyright 2004 Wiley-Liss, Inc.