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 Comparison of Fgf10+ expressing cell mRNA profiles from submandibular glands of 7 day old pups and 60 days old mice in duplicate

唾液腺是一类不可或缺的结构，可向口腔分泌唾液并维持口腔健康。小鼠与人类的唾液腺发育受间质表达的成纤维细胞生长因子10（fibroblast growth factor-10, FGF10）调控。本研究借助唾液腺单细胞RNA测序（single cell RNA-seq）图谱，以及他莫昔芬诱导型Fgf10CreERT2:R26-tdTomato小鼠模型，证实FGF10阳性细胞（FGF10pos）在出生后第5天（P5）前仅以间质来源形式存在；而在出生后第7天（P7）后，其表达谱系发生转换，至出生后第15天（P15）后仅能检测到上皮来源的FGF10阳性细胞。对分选得到的间质与上皮来源FGF10阳性细胞进行进一步RNA测序分析后发现，上皮来源的FGF10阳性细胞群体表达古老离子细胞的特征标志物Foxi1、Foxi2、Ascl3，以及囊性纤维化跨膜传导调节因子（cystic fibrosis transmembrane conductance regulator, CFTR）。本研究提出，上皮来源的FGF10阳性细胞为特化的唾液腺离子细胞，在唾液的离子修饰过程中发挥重要作用。此外，它们可通过与表达成纤维细胞生长因子受体2b（FGFR2b）的上皮祖细胞及肌上皮细胞进行通信，维持FGF10依赖型腺体的稳态。本研究还对7日龄幼鼠与60日龄成年小鼠下颌下腺中Fgf10阳性细胞的mRNA表达谱开展了双重复比较分析。