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...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 RNAsequencing 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.展开更多
基金supported by the Natural Science Foundation of China (81974443)Natural Science Foundation of Guangdong Province (2018A030313176)+1 种基金Open Funding of the State Key Laboratory of Oral Diseases (SKLOD2021OF02)Guangdong Basic and Applied Basic Research Foundation (2019A1515110110)。
文摘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 RNAsequencing 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.
