Abstract
The secretory acinar cells of the salivary gland are essential for saliva secretion, but are also the cell type preferentially lost following radiation treatment for head and neck cancer. The source of replacement acinar cells is currently a matter of debate. There is evidence for the presence of adult stem cells located within specific ductal regions of the salivary glands, but our laboratory recently demonstrated that differentiated acinar cells are maintained without significant stem cell contribution. To enable further investigation of salivary gland cell lineages and their origins, we generated three cell-specific Cre driver mouse strains. For genetic manipulation in acinar cells, an inducible Cre recombinase (Cre-ER) was targeted to the prolactin-induced protein (Pip) gene locus. Targeting of the Dcpp1 gene, encoding demilune cell and parotid protein, labels intercalated duct cells, a putative site of salivary gland stem cells, and serous demilune cells of the sublingual gland. Duct cell-specific Cre expression was attempted by targeting the inducible Cre to the Tcfcp2l1 gene locus. Using the R26Tomato Red reporter mouse, we demonstrate that these strains direct inducible, cell-specific expression. Genetic tracing of acinar cells using PipGCE supports the recent finding that differentiated acinar cells clonally expand. Moreover, tracing of intercalated duct cells expressing DcppGCE confirms evidence of duct cell proliferation, but further analysis is required to establish that renewal of secretory acinar cells is dependent on stem cells within these ducts.
Highlights
The salivary glands are responsible for the secretion of saliva, which is essential for oral health
In contrast to the endogenous expression of prolactin-induced protein (Pip) in parotid, sublingual and lacrimal glands (S1 Fig)[20], there was no evidence of Cre activation in these tissues (Fig 2C–2E)
To ascertain the cell type expressing PipGCE, sections of submandibular gland (SMG) were co-stained with antibody to Nkcc1, which labels acinar cell membranes (Fig 2F)
Summary
The salivary glands are responsible for the secretion of saliva, which is essential for oral health. The major cellular component of the salivary glands is the secretory acinar cells (reviewed in [1]), which are arranged in clusters. The acinar cells secrete primary saliva into the small, intercalated ducts, which are linked to striated ducts. The saliva is conducted through the ductal tree to the large excretory ducts, which empty into the oral cavity (Fig 1). A decrease in PLOS ONE | DOI:10.1371/journal.pone.0146711. A decrease in PLOS ONE | DOI:10.1371/journal.pone.0146711 January 11, 2016
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