Fig 1: SG FGF10pos ionocytes maintain growth of epithelial cells and saliva homeostasis(A) Experimental setup: SG FGF10pos ionocytes were isolated from the Fgf10CreERT2:R26-tdTomato mice, and SG MECs from the aSMA-GFP mice. Matrigel mixed with or without ionocytes was spread on a glass-bottomed dish and MECs were plated on top. After 48 h culture, cells were immunostained with P-H3 antibody (proliferation marker) and DAPI. P-H3pos nuclei within MECs were quantified.(B) Plots (mean ± SD) comparing the proportion of proliferating cells in control (MECs, n = 10) and experimental (MECs + ionocytes, n = 10) conditions (n, number of replicates). Statistical significance was assessed with an unpaired t test (***p < 0.001).(C) Experimental setup: lacrimal EPCPs and SMG FGF10pos cells were isolated and grown in vitro either alone (controls) or mixed in a 1:1 ratio.(D) Isolated SMG FGF10pos ionocytes increase growth of lacrimal gland epithelial cell progenitors (EPCPs). Cells reaggregate and their size was measured from 1 to 7 days (40–50 aggregates per each condition/time point; mean ± SD, two-tailed Fisher’s exact test; *p < 0.05, **p < 0.01,***p < 0.001).(E) Schematic of ionocyte prior to induction of Fgf10 expression. Neonatal Ascl3pos cells in SMGs are not fully differentiated and express fewer ion transporter genes.(F) List of common and unique transporters between developing and mature ionocytes.(G) Schematic showing differentiated SMG ionocytes where active Na+ absorption is likely driven through the NHE4 (Slc9a4), NKCC1 (Slc12a2), and Na+/K+-ATPases (Atp1a1 and/or Atp1b) in the basolateral membrane creating passive Cl- transport. Secretion is driven by Cl- and NCO- secretion through CFTR and other Cl- channels in the apical membrane. Active Cl- secretion creates Na+ and water movement across the epithelium paracellularly and/or transcellularly.(H) Function of FGF10 in SG duct epithelium. FGF10pos ionocytes signal to FGFR2bpos cells, such as basal duct, MEC, and EGFpos cells in a paracrine fashion. FGF10 released from ionocytes maintain cell viability and plasticity. Models were created using Biorender. All bar plots are presented as mean ± SD.