A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10 ^CreERT2 :R26-tdTomato mouse, we show that FGF10^pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10^pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10^pos cells shows that the epithelial FGF10^pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1 , Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10^pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2b^pos ductal and myoepithelial cells. [Display omitted] Our study demonstrates that, during early postnatal development, FGF10 is expressed by mesenchymal fibroblasts and signals to SG epithelium, which contains immature ionocytes expressing Cftr, Ascl3, and Foxi1. Between P5 and P15, the shift of FGF10 expression from mesenchymal to epithelial cells is observed. Importantly, this FGF10 expression shift correlates with ionocyte maturation. The mature FGF10^pos ionocytes express more ion channels and participate in the ionic modification of saliva. Ionocyte-derived FGF10 is predicted to signal to myoepithelial cells and basal duct cells. • Unique FGF10-expressing ionocytes have been identified within salivary gland ducts • The FGF10^pos ionocytes express the hallmark of ancient ionocyte signature genes • FGF10 expression shifts from fibroblasts to ionocytes between postnatal days 7 and 15 • Salivary gland ionocytes maintain ion homeostasis and act as niche cells Mauduit et al. identified unique FGF10-expressing ionocytes in salivary glands. FGF10 expression shifts from fibroblasts to epithelial ionocytes during postnatal development. Ionocytes play a dual role in salivary gland homeostasis; they maintain specific ion composition in saliva and act as niche cells, providing growth factor support for other epithelial cells. [ABSTRACT FROM AUTHOR]