TY - JOUR
T1 - Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands
AU - NIDCD/NIDCR Genomics and Computational Biology Core
AU - Rheinheimer, Brenna A.
AU - Pasquale, Mary C.
AU - Limesand, Kirsten H.
AU - Hoffman, Matthew P.
AU - Chibly, Alejandro M.
N1 - Funding Information:
The authors thank the support from Dr. Daniel Martin, Dr. Robert Morell, and Dr. Erich Boger from the Genomics and computational biology core (GCBC) at NIDCR 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. Conceptualization, writing and editing, A.M.C. B.R. K.H.L. and M.P.H; Methodology, A.M.C. B.R. M.C.P. G.C.B.C. and M.P.H; Software, A.M.C. and G.C.B.C.; Resources, M.P.H. K.H.L. and A.M.C.; Visualization, A.M.C. B.R. and M.C.P.; Data curation, project administration, and supervision, A.M.C. The authors declare no competing interests.
Funding Information:
The authors thank the support from Dr. Daniel Martin, Dr. Robert Morell, and Dr. Erich Boger from the Genomics and computational biology core (GCBC) at NIDCR 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 .
Publisher Copyright:
© 2023
PY - 2023/5/19
Y1 - 2023/5/19
N2 - Understanding the transcriptional landscape that results in chronic salivary hypofunction after irradiation will help identify injury mechanisms and develop regenerative therapies. We present scRNA-seq analysis from control and irradiated murine parotid glands collected 10 months after irradiation. We identify a population of secretory cells defined by specific expression of Etv1, which may be an acinar cell precursor. Acinar and Etv1+ secretory express Ntrk2 and Erbb3, respectively while the ligands for these receptors are expressed in myoepithelial and stromal cells. Furthermore, our data suggests that secretory cells and CD4+CD8+T-cells are the most transcriptionally affected during chronic injury with radiation, suggesting active immune involvement. Lastly, evaluation of cell-cell communication networks predicts that neurotrophin, neuregulin, ECM, and immune signaling are dysregulated after irradiation, and thus may play a role in the lack of repair. This resource will be helpful to understand cell-specific pathways that may be targeted to repair chronic damage in irradiated glands.
AB - Understanding the transcriptional landscape that results in chronic salivary hypofunction after irradiation will help identify injury mechanisms and develop regenerative therapies. We present scRNA-seq analysis from control and irradiated murine parotid glands collected 10 months after irradiation. We identify a population of secretory cells defined by specific expression of Etv1, which may be an acinar cell precursor. Acinar and Etv1+ secretory express Ntrk2 and Erbb3, respectively while the ligands for these receptors are expressed in myoepithelial and stromal cells. Furthermore, our data suggests that secretory cells and CD4+CD8+T-cells are the most transcriptionally affected during chronic injury with radiation, suggesting active immune involvement. Lastly, evaluation of cell-cell communication networks predicts that neurotrophin, neuregulin, ECM, and immune signaling are dysregulated after irradiation, and thus may play a role in the lack of repair. This resource will be helpful to understand cell-specific pathways that may be targeted to repair chronic damage in irradiated glands.
KW - Cell biology
KW - Immunology
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85153603744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85153603744&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106660
DO - 10.1016/j.isci.2023.106660
M3 - Article
AN - SCOPUS:85153603744
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 5
M1 - 106660
ER -