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

Salivary glands are essential structures that secrete saliva to the oral cavity and maintain oral health. Development of salivary glands in mice and humans is controlled by mesenchymally expressed fibroblast growth factor-10 (FGF10). Using single cell RNA-seq atlas of the salivary gland and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5), but after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNAseq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos populations express the hallmark of ancient ionocyte signature Foxi1, Foxi2, Ascl3 and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized salivary gland ionocytes that are important for the ionic modification of saliva. In addition, they maintain FGF10-dependent glands homeostasis via communication with FGFR2b-expressing epithelial progenitor and myoepithelial cells Overall design: Comparison of Fgf10+ expressing cell mRNA profiles from submandibular glands of 7 day old pups and 60 days old mice in duplicate

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Mauduit O, Aure MH, Delcroix V, Basova L, Srivastava A, Umazume T, Mays JW, Bellusci S, Tucker AS, Hajihosseini MK, Hoffman MP, Makarenkova HP