Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands.

Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands.
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DOI:
10.1016/j.isci.2023.106660
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发表时间:
2023-05-19
期刊:
影响因子:
5.8
通讯作者:
Chibly, Alejandro M.
Chibly, Alejandro M.
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Rheinheimer, Brenna A.;Pasquale, Mary C.;Limesand, Kirsten H.;Hoffman, Matthew P.;Chibly, Alejandro M.

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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. Etv1 defines a discrete cluster of secretory cells that may be acinar precursors Ntrk2 and Erbb3 are highly specific secretory cell receptors CD4+CD8+T-cells and acinar cells have the greatest transcriptional changes after IR Ntrk2, Erbb3, ECM, and immune signaling are altered in secretory cells after IR Cell biology; Immunology; Transcriptomics
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