Radiotherapy-induced esophageal toxicity(RIET)is a common dose-limiting complication in thoracic radiotherapy with limited treatment options.RIET is a multifactorial process involving diverse cell types within a compl...Radiotherapy-induced esophageal toxicity(RIET)is a common dose-limiting complication in thoracic radiotherapy with limited treatment options.RIET is a multifactorial process involving diverse cell types within a complex tissue structure.Single-cell RNA sequencing(scRNA-Seq)offers high-resolution insights into tissue heterogeneity.It has been successfully applied to radiation-related injuries in the skin,brain,intestine,and lung1,revealing pathogenic mechanisms and laying a mechanistic foundation for targeted drug discovery2,3,4.However,no scRNA-Seq-based investigations of RIET have yet been reported.To fill this gap,we established RIET rat models using both single-and fractionated-irradiation protocols and generated the first single-cell transcriptomic atlas of RIET in rats.We identified nine major cell types exhibiting distinct transcriptional dynamics,and integrative analyses uncovered shared differentially expressed genes,signaling pathways,and cell–cell communication networks involved in RIET self-remodeling.Guided by these insights,we conducted mechanism-driven drug screening and identified three candidate agents with both radioprotective and radiosensitizing properties(Fig.1A).展开更多
基金supported by the National Natural Science Foundation of China(82473568 and U25A20151)the Young Talent Project of China National Nuclear Corporation(CNNC202379)+1 种基金Foundation of Department of Science and Technology of Sichuan Provincial(2024NSFSC0764,China)the Open Project of Sichuan Clinical Research Center for Radiation and Therapy,the Second Affiliated Hospital of Chengdu Medical College,Nuclear Industry 416 Hospital(2024ZX02 and 2024ZX05,China).
文摘Radiotherapy-induced esophageal toxicity(RIET)is a common dose-limiting complication in thoracic radiotherapy with limited treatment options.RIET is a multifactorial process involving diverse cell types within a complex tissue structure.Single-cell RNA sequencing(scRNA-Seq)offers high-resolution insights into tissue heterogeneity.It has been successfully applied to radiation-related injuries in the skin,brain,intestine,and lung1,revealing pathogenic mechanisms and laying a mechanistic foundation for targeted drug discovery2,3,4.However,no scRNA-Seq-based investigations of RIET have yet been reported.To fill this gap,we established RIET rat models using both single-and fractionated-irradiation protocols and generated the first single-cell transcriptomic atlas of RIET in rats.We identified nine major cell types exhibiting distinct transcriptional dynamics,and integrative analyses uncovered shared differentially expressed genes,signaling pathways,and cell–cell communication networks involved in RIET self-remodeling.Guided by these insights,we conducted mechanism-driven drug screening and identified three candidate agents with both radioprotective and radiosensitizing properties(Fig.1A).
