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

Mauduit, Olivier, Aure, Marit H., Delcroix, Vanessa, Basova, Liana, Srivastava, Amrita, Umazume, Takeshi, Mays, Jacqueline W., Bellusci, Saverio, Tucker, Abigail S., Hajihosseini, Mohammad K., Hoffman, Matthew P. and Makarenkova, Helen P. (2022) A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands. Cell Reports, 39 (2). ISSN 2211-1247

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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.

Item Type: Article
Additional Information: H.P.M., O.M., V.D., A.S., L.B., and T.U. were supported by the National Eye Institute (NEI), United States, grants 5R01EY026202 and 5R01EY028983, and NIDCR grant R01DE031044. S.B. was supported by the Cardio-Pulmonary Institute and by grants from the Deutsche Forschungsgemeinschaft (DFG) (BE4443/1-1, BE4443/4-1, BE4443/6-1, KFO309 P7, and SFB1213 projects A02 and A04). M.P.H., J.W.M., and M.H.A. were supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH. The graphical abstract was created using Biorender.
Uncontrolled Keywords: cftr,cp: developmental biology,fgf10,fgfr2b signaling,foxi1,duct cells,ionocytes,niche cells,salivary gland,single-cell rna sequencing,submandibular gland,biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 20 Apr 2022 15:30
Last Modified: 23 Oct 2022 03:43
URI: https://ueaeprints.uea.ac.uk/id/eprint/84699
DOI: 10.1016/j.celrep.2022.110663

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