Neurotrophin signaling is a central mechanism of salivary dysfunction after irradiation that disrupts myoepithelial cells.

"all code to download and process the bulk rnaseq data as well as the single-cell rnaseq datasets from the smg atlas and tabula sapiens has been deposited to a publicly available repository located in https://github com/chiblya/ir_salivaryglands . the color scale represents scaled gene expression values *long non-coding rnas small nuclear rnas snoras and other pseudogenes were overrepresented among downregulated genes and were removed from heatmap (see supplementary data 1 for complete list); a representative expression profile is shown at the bottom of the heatmaps.; we identified 1643 degs in ir-pg and 1471 degs in ir-smg and heatmaps of the 25 most highly down and upregulated genes are shown (fig 1c all data in supplementary data 1 ).; only one representative gene was included in deg heatmaps and the rest are listed in supplementary data 1 .; other genes that were upregulated included ascl3 a marker of salivary ionocytes and lrg5 which marks progenitor cells in the intestine - as well as members of the frizzled family ( frzb and sfrp2 ) associated with mesenchymal wnt signaling (supplementary data 1 ).; using ingenuity pathway analysis (ipa) software we identified 102 signaling pathways overrepresented in the ir-pg degs and 65 pathways in ir-smg degs (supplementary tables1 and 2 supplementary data 2 ) and focused on the common ir-dysregulated pathways across both glands.; because signaling pathways are often triggered by the interaction between cell receptors with their respective ligands and culminate in the activation of transcription factors to regulate gene expression we limited our prediction of upstream regulators to growth factors receptors and transcription factors (supplementary table 3 supplementary data 3 ).; supplementary figures1-7 supplementary data 1 - differentially expressed genes.; supplementary data 2 - pathway analysis supplementary data 3- upstream regulator analysis reporting summary publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. data availability the rnaseq data used for the study are deposited to geneexpression omnibus (gse206878"

"analysis and plots generated with the ligandreceptor script available on github ( https://github com/chiblyaa/ligandreceptor ).; all code to download and process the bulk rnaseq data as well as the single-cell rnaseq datasets from the smg atlas and tabula sapiens has been deposited to a publicly available repository located in https://github com/chiblya/ir_salivaryglands .; software used for analysis is reported in supplementary table 7 and all r packages and versions used for scripted analyses are listed in the github repository. software used for analysis is reported in supplementary table 7 and all r packages and versions used for scripted analyses are listed in the github repository."

"Competing interests The authors declare no competing interests."

"The authors thank the support from Dr. Daniel Martin, Dr. Robert Morell, and Dr. Erich Boger from the NIDCD/NIDCR Genomics and Computational Biology Core for contributing to library preparation and sequencing. This work used the NIDCR Veterinary Resources Core (ZIC DE000740–05) and computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). The GCBC funds were from the NIDCD Division of Intramural Research/NIH (DC000086 to the GCBC). The study was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH."