Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages

ABSTRACT To analyze cell lineage in the pancreatic islets, we have irreversibly tagged all the progeny of cells through the activity of Cre recombinase. Adult glucagon (α) and insulin (β) cells are shown to derive from cells that have never transcribed insulin or glucagon, respectively. Also, the β-cell progenitors, but not α-cell progenitors, transcribe the pancreatic polypeptide (PP) gene. Finally, the homeodomain gene PDX1, which is expressed by adult β-cells, is also expressed by α-cell progenitors. Thus the islet α- and β-cell lineages appear to arise independently during ontogeny, probably from a common precursor.