味觉类器官在化疗药物导致的味觉损伤疾病治疗中的应用

Normal taste system is basis for nutrition intake and maintenance of physiological function in human body. Taste dysfunction resulted from chemotherapy drugs is a common symptom in cancer patients. However, the molecular mechanism underlying taste dysfunction is still not clear. In the previous studies, applicant established taste organoid in vitro culture system, which provided an ideal model for the study on regulation of taste cell differentiation and therapy against taste disorders. Thus, using both transgenic mice model marking Lgr5+ taste stem cells and taste organoids in vitro model, this proposal focus on analyzing the various phenotypes as well as behavioral and physiological characteristics of taste dysfunction, including the alteration in stem cell proliferation and differentiation, apoptotic signaling pathway, inflammatory factors and taste nerve function. The critical genes as well as signaling pathways involved in chemotherapy drugs-induced taste dysfunction will be identified by RNA-Seq. We will also restore the taste cells or taste stem cells in vitro to elucidate the mechanism underlying taste dysfunction. This project will provide experimental and theoretical basis to recovery of taste dysfunction using taste organoids.

正常的味觉系统是机体用来摄取营养和维持正常生理功能的基础。因化疗药物导致的味觉损伤是癌症患者的常见症状，但味觉损伤的具体分子机制尚不明了。在前期的研究中，申请人建立了味觉类器官培养系统，这为研究味觉细胞的分化调控以及味觉疾病的治疗提供了理想的研究模型。因此，本研究将以标记Lgr5阳性味觉干细胞的转基因小鼠为在体实验模型，并以培养的味觉类器官为离体实验模型，分析味觉损伤的各种表型以及行为学和生理学特征，包括干细胞增殖/分化的变化、凋亡信号通路、炎症因子以及对味觉神经功能的影响等。同时借助RNA转录组测序和基因组学比对筛选化疗药物导致味觉损伤的关键基因和涉及的关键信号通路，通过在体外修复受损味觉细胞/干细胞阐述味觉受损的机制。本项目的研究成果将为利用味觉类器官来修复受损味觉提供实验基础和理论依据。