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Myoepithelial (ME) cells in exocrine glands exhibit both epithelial and mesenchymal features, contributing to fluid secretion through contraction. However, the regulation mechanism of behind this unique phenotype in salivary glands remains unclear. We established a flow cytometry-based purification method using cell surface molecules, epithelial cell adhesion molecule (EpCAM) and alpha 6 integrin (CD49f), to characterize ME cells. EpCAM+CD49fhighcells showed relatively high expression of ME cell-marker genes, such as alpha-smooth muscle actin (α-SMA). For lineage tracing and strict isolation, tdTomato+EpCAM+CD49fhigh-ME cells were obtained from myosin heavy chain 11 (Myh11) -CreERT2/tdTomato mice. Transcriptome analysis revealed that expression of genes involved in the epithelial-mesenchymal transition, including Snai2, were upregulated in the ME cell-enriched subset. Snai2suppression in stable ME cells decreased α-SMAand increased Krt14expression, suggesting that ME cell features may be controlled by the epithelial-mesenchymal balance regulated by Snai2. In contrast, ME cells showed reduced ME properties and expressed the ductal markers Krt18/19under sphere culture conditions. Notch signaling was activated under sphere culture conditions; excessive activation of Notch signaling accelerated Krt18/19expression, but reduced α-SMAand Snai2expression, suggesting that the behavior of Snai2-expressing ME cells may be controlled by Notch signaling.

Myoepithelial (ME) cells in exocrine glands exhibit both epithelial and mesenchymal features, contributing to fluid secretion through contraction. However, the regulation mechanism of behind this unique phenotype in salivary glands remains unclear. We established a flow cytometry-based purification method using cell surface molecules, epithelial cell adhesion molecule (EpCAM) and alpha 6 integrin (CD49f), to characterize ME cells. EpCAM+CD49fhighcells showed relatively high expression of ME cell-marker genes, such as alpha-smooth muscle actin (α-SMA). For lineage tracing and strict isolation, tdTomato+EpCAM+CD49fhigh-ME cells were obtained from myosin heavy chain 11 (Myh11) -CreERT2/tdTomato mice. Transcriptome analysis revealed that expression of genes involved in the epithelial-mesenchymal transition, including Snai2, were upregulated in the ME cell-enriched subset. Snai2suppression in stable ME cells decreased α-SMAand increased Krt14expression, suggesting that ME cell features may be controlled by the epithelial-mesenchymal balance regulated by Snai2. In contrast, ME cells showed reduced ME properties and expressed the ductal markers Krt18/19under sphere culture conditions. Notch signaling was activated under sphere culture conditions; excessive activation of Notch signaling accelerated Krt18/19expression, but reduced α-SMAand Snai2expression, suggesting that the behavior of Snai2-expressing ME cells may be controlled by Notch signaling.

Aging-related salivary gland changes, such as lymphocyte infiltration and acinar cell loss decrease saliva secretion, thereby affecting quality of life. The precise molecular mechanisms underlying these changes remain unclear.

Organogenesis is regulated by morphogen signaling and transcription networks. These networks differ between organs, and identifying the organ-specific network is important to clarify the molecular mechanisms of development and regeneration of organs. Several studies have been conducted to identify salivary gland-specific networks using a mouse submandibular gland model. The submandibular glands (SMGs) of mice manifest as a thickening of the oral epithelium at embryonic day 11.5 and invaginate into the underlying mesenchyme. The network between Fgf10 and Sox9 is involved in SMG development in mice.