Sox9<sup>+</sup> cells are required for salivary gland regeneration after radiation damage via the Wnt/β-catenin pathway

Xiuyun Xu; Gan Xiong; Ming Zhang; Jiaxiang Xie; Shuang Chen; Kang Li; Jingting Li; Yong Bao; Cheng Wang; Demeng Chen

doi:10.1016/j.jgg.2021.09.008

Volume 49 Issue 3

Mar. 2022

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Article Navigation > Journal of Genetics and Genomics > 2022 > 49(3): 230-239

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Sox9⁺ cells are required for salivary gland regeneration after radiation damage via the Wnt/β-catenin pathway

doi: 10.1016/j.jgg.2021.09.008

a Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510030, China;
b Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China;
c Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China

Funds:

This work was supported by the Natural Science Foundation of China (81974443), Natural Science Foundation of Guangdong Province (2018A030313176), Open Funding of the State Key Laboratory of Oral Diseases (SKLOD2021OF02) and Guangdong Basic and Applied Basic Research Foundation (2019A1515110110). We appreciate Rongsong Ling for professional advice on the data analysis.

Received Date: 2021-07-16
Accepted Date: 2021-09-30
Rev Recd Date: 2021-09-29
Publish Date: 2021-10-28

Abstract

Abstract

Radiotherapy for head and neck cancer can cause serious side effects, including severe damage to the salivary glands, resulting in symptoms such as xerostomia, dental caries, and oral infection. Because of the lack of long-term treatment for the symptoms of xerostomia, current research has focused on finding endogenous stem cells that can differentiate into various cell lineages to replace lost tissues and restore functions. Here, we report that Sox9⁺ cells can differentiate into various salivary epithelial cell lineages under homeostatic conditions. After ablating Sox9⁺ cells, the salivary glands of irradiated mice showed more severe phenotypes and the reduced proliferative capacity. Analysis of online single-cell RNA-sequencing data reveals the enrichment of the Wnt/β-catenin pathway in the Sox9⁺ cell population. Furthermore, treatment with a Wnt/β-catenin inhibitor in irradiated mice inhibits the regenerative capability of Sox9⁺ cells. Finally, we show that Sox9⁺ cells are capable of forming organoids in vitro and that transplanting these organoids into salivary glands after radiation partially restored salivary gland functions. These results suggest that regenerative therapy targeting Sox9⁺ cells is a promising approach to treat radiation-induced salivary gland injury.
- Radiation-induced salivary gland injury,
- Sox9,
- Wnt/β-catenin pathway,
- Regeneration,
- Organoids

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References(29)

References

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