Progenitor/Stem Cell Function During Salivary Gland Development

National Institute Of Dental & Craniofacial Research

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Abstract

Fibroblast growth factor 10 (FGF10), a well established mesenchyme-derived growth factor critical for progenitor cell proliferation and expansion during fetal organogenesis in mice and humans. In order to investigate salivary rogenitor cell identities, lineage relationships and functions of we generated a single-cell RNAseq analysis at multiple stages of murine salivary gland development. This project provided us with an atlas of the transcriptional landscape of murine salivary gland development. Using the single cell RNA-sequencing atlas and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse we showed that FGF10-expressing cells are exclusively mesenchymal until postnatal day 5 but after P7, there is a switch in expression and only epithelial FGF10-expressing cells are observed after P15. Further RNAseq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10-expressing population express the hallmark 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-expressing cells are specialized salivary gland ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2b-expressing duct and myoepithelial cells.