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

Olivier Mauduit, Marit H. Aure, Vanessa Delcroix, Liana Basova, Amrita Srivastava, Takeshi Umazume, Jacqueline W. Mays, Saverio Bellusci, Abigail S. Tucker, Mohammad K. Hajihosseini, Matthew P. Hoffman, Helen P. Makarenkova

Research output: Contribution to journalArticlepeer-review

2 Downloads (Pure)

Abstract

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 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 RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hall- marks 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 FGF10pos 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 FGFR2bpos ductal and myoepithelial cells.
Original languageEnglish
Article number110663
JournalCell Reports
Volume39
Issue number2
Early online date13 Apr 2022
DOIs
Publication statusPublished - Apr 2022

Keywords

  • CFTR
  • CP: Developmental biology
  • FGF10
  • FGFR2b signaling
  • Foxi1
  • duct cells
  • ionocytes
  • niche cells
  • salivary gland
  • single-cell RNA sequencing
  • submandibular gland

Cite this