Ascl3 expression marks progenitor cells in the mouse salivary glands

Objectives: The ducts are the putative site of progenitor cells in the adult salivary gland, but a lack of specific markers has impeded the identification and isolation of such cells. Ascl3, also know as Sgn1, is a member of the mammalian achaete scute (Mash) gene family of transcription factors, which have been implicated in cell fate specification and differentiation. In the mouse salivary gland, expression of Ascl3 is restricted to a subset of duct cells. Methods: Using a Cre recombinase-mediated reporter system in mice, we followed the fate of Ascl3-expressing cells after the introduction of an EGFP-Cre expression cassette into the Ascl3 locus by homologous recombination. Immunohistochemistry and BrdU incorporation were used to characterize the Ascl3-expressing cells and their descendants. Results: Lineage tracing shows that these cells are progenitors of both acinar and ductal cell types in all three major salivary glands. Ascl3-expressing cells incorporate BrdU, and are therefore dividing, but differentiation of these cells is accompanied by down regulation of Ascl3 expression. Our data directly demonstrate a progenitor-progeny relationship between a subpopulation of cells in the duct and descendants in the acinar cell compartment. Conclusions: Although they are not stem cells, the Ascl3-expressing cells are multipotent; capable of generating acinar, demilune and ductal cell types. We conclude that Ascl3 marks an intermediate cell type, derived from adult stem cells, that is responsible for tissue maintenance in the mature salivary glands. This work was supported by NIH/NIDCR grant R21 DE017386.