The Transcriptional Co-Activator Taz Contributes to the Differentiation of a Salivary Gland Epithelial Cell Line Towards a Myoepithelial Phenotype

Myoepithelial cells serve as contractile units in exocrine glands, including mammary, salivary, and lacrimal glands, and their dysfunction negatively impacts secretory function. In spite of their importance, mechanisms that regulate myoepithelial differentiation are poorly defined. To study this process, we employed an established murine salivary gland epithelial cell line, mSG-PAC-1, that we previously demonstrated recapitulates aspects of acinar cell differentiation when cultured as spheroids. Here, we report that mSG-PAC1 spheroids can be induced towards a myoepithelial phenotype by manipulating culture conditions, resulting in the inhibition of expression of the acinar marker, AQP5, the upregulation of myoepithelial markers SMA, calponin, and the integrin {beta}4 subunit, as well as the acquisition of myoepithelial morphology. Transcriptome analysis indicated that YAP/TAZ target genes are also upregulated. We demonstrate that the transcriptional co-activator TAZ is expressed by the same cells that express SMA in the epithelial compartment of the differentiating murine salivary gland and by mSG-PAC1 cells under conditions that promote a myoepithelial phenotype. Furthermore, siRNA targeting TAZ expression in mSG-PAC1 spheroids diminishes expression of myoepithelial markers, implicating TAZ in their regulation. Thus, we have demonstrated mSG-PAC1 cells are a reliable tool to complement in vivo approaches to understand mechanisms that promote myoepithelial differentiation. Summary StatementIdentification of a transcriptional co-regulator as a contributor to myoepithelial differentiation in three-dimensional cell culture