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Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.

ABSTRACT: 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. Salivary gland function depends on the secretory acinar cells, which are responsible for saliva formation, and duct cells, which modify the saliva and conduct it to the oral cavity. The salivary gland ducts are also the putative site of progenitor cells in the adult gland. Using a Cre recombinase-mediated reporter system, we followed the fate of Ascl3-expressing cells after the introduction of an EGFP-Cre expression cassette into the Ascl3 locus by homologous recombination. Lineage tracing shows that these cells are progenitors of both acinar and ductal cell types in all three major salivary glands. In the differentiated progeny, expression of Ascl3 is down-regulated. These data directly demonstrate a progenitor-progeny relationship between duct cells and the acinar cell compartment, and identify a population of multipotent progenitor cells, marked by expression of Ascl3, which is capable of generating both gland cell types. We conclude that Ascl3-expressing cells contribute to the maintenance of the adult salivary glands.

SUBMITTER: Bullard T

PROVIDER: S-EPMC2570651 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.

Bullard Tara T Koek Laurie L Roztocil Elisa E Kingsley Paul D PD Mirels Lily L Ovitt Catherine E CE

Developmental biology 20080423 1

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. Salivary gland function depends on the secretory acinar cells, which are responsible for saliva formation, and duct cells, which modify the saliva and conduct it to the oral cavity. The salivary gland ducts are also the p ...[more]

PMID: 18572159

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Project description:Understanding the mechanisms of controlled expansion and differentiation of basal progenitor cell populations during organogenesis is essential for developing targeted regenerative therapies. Since the cytokeratin 5-positive (K5+) basal epithelial cell population in the salivary gland is regulated by retinoic acid signaling, we interrogated how isoform-specific retinoic acid receptor (RAR) signaling impacts the K5+ cell population during salivary gland organogenesis to identify RAR isoform-specific mechanisms that could be exploited in future regenerative therapies. In this study, we utilized RAR isoform-specific inhibitors and agonists with murine submandibular salivary gland organ explants. We determined that RAR? and RAR? have opposing effects on K5+ cell cycle progression and cell distribution. RAR? negatively regulates K5+ cells in both whole organ explants and in isolated epithelial rudiments. In contrast, RAR? is necessary but not sufficient to positively maintain K5+ cells, as agonism of RAR? alone failed to significantly expand the population. Although retinoids are known to stimulate differentiation, K5 levels were not inversely correlated with differentiated ductal cytokeratins. Instead, RAR? agonism and RAR? inhibition, corresponding with reduced K5, resulted in premature lumenization, as marked by prominin-1. With lineage tracing, we demonstrated that K5+ cells have the capacity to become prominin-1+ cells. We conclude that RAR? and RAR? reciprocally control K5+ progenitor cells endogenously in the developing submandibular salivary epithelium, in a cell cycle-dependent manner, controlling lumenization independently of keratinizing differentiation. Based on these data, isoform-specific targeting RAR? may be more effective than pan-RAR inhibitors for regenerative therapies that seek to expand the K5+ progenitor cell pool.RAR? and RAR? reciprocally control K5+ progenitor cell proliferation and distribution in the developing submandibular salivary epithelium in a cell cycle-dependent manner while regulating lumenization independently of keratinizing differentiation.

Dataset Information

Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.

Publications

Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.

Similar Datasets

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