RT Journal Article
SR Electronic
T1 scRNAseq comparison of healthy and irradiated mouse parotid glands highlights immune involvement during chronic gland dysfunction
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.26.517939
DO 10.1101/2022.11.26.517939
A1 Rheinheimer, Brenna
A1 Pasquale, Mary C.
A1 ,
A1 Limesand, Kirsten H.
A1 Hoffman, Matthew P.
A1 Chibly, Alejandro M
YR 2022
UL http://biorxiv.org/content/early/2022/11/26/2022.11.26.517939.abstract
AB Translational frameworks to understand the chronic loss of salivary dysfunction that follows after clinical irradiation, and the development of regenerative therapies remain an unmet clinical need. Understanding the transcriptional landscape long after irradiation treatment that results in chronic salivary hypofunction will help identify injury mechanisms and develop regenerative therapies to address this need. Advances in single cell (sc)RNAseq have made it possible to identify previously uncharacterized cell types within tissues and to uncover gene regulatory networks that mediate cell-cell communication and drive specific cell states. scRNAseq studies have been performed for virtually all major tissues including salivary glands; however, there are currently no scRNAseq studies the long-term chronic effects of irradiation on salivary glands. Here, we present scRNAseq from control and irradiated murine parotid glands collected 10 months post-irradiation. We identify a previously uncharacterized population of epithelial cells in the gland defined by expression of Etv1, which may be an acinar cell precursor. These Etv1+ cells also express Ntrk2 and Erbb3 and thus may respond to myoepithelial cell-derived growth factor ligands. Furthermore, our data suggests that CD8+ T-cells and secretory cells are the most transcriptionally affected during chronic injury with radiation, suggesting active immune involvement during chronic injury post-irradiation. Thus, our study provides a resource to understand the transcriptional landscape in a chronic post-irradiation microenvironment and identifies cell-specific pathways that may be targeted to repair chronic damage.HIGHLIGHTSWe generated a scRNAseq dataset of chronic post-irradiation injury in parotid glandsA newly identified Etv1+ epithelial population may be acinar precursorsNtrk2 and Erbb3 are highly specific Etv1+ cell receptors that may mediate cell-cell communication with myoepithelial cellsCD8+ T-cells and secretory acinar cells have the greatest transcriptional changes post-IRCompeting Interest StatementThe authors have declared no competing interest.