基于单细胞测序技术对Pax8在碘致甲状腺肿中调控机制的研究

甲状腺肿是甲状腺疾病中最常见的一种疾病，碘营养不良是该疾病的主要致病因素之一。随着全民食盐加碘政策的持续实施，我国居民碘营养状况得到了根本性改善，但甲肿问题仍然威胁人群健康。有证据表明，甲肿有恶变为甲状腺癌的潜能，并且甲肿患者罹患甲癌的风险也显著高于正常人群，预防甲肿的发生可有效降低甲状腺癌的风险，有利于实现疾病的早期预防。申请者前期发现Pax8在甲肿中的重要调控作用，并成功构建了Pax8 cre-loxp模型动物，基于前期研究基础拟采用单细胞测序技术探索甲肿相关的差异表达基因，同时与甲状腺癌的基因组特征比对分析，以Pax8为重点研究目标，观察不同水平碘所致甲肿的遗传学特点，分析甲肿进展甲状腺癌的潜在基因及作用机制，为阐明甲肿发生发展的遗传学机制提供科学依据，也为了解甲肿向甲状腺癌恶变的遗传危险特征以及甲状腺癌的发生发展机制奠定基础，本项目的研究成果对甲状腺疾病的防治具有重要实用价值。

Goiter is one of the most common thyroid diseases. Iodine malnutrition is an independent risk factor for the development of goiter. As the implementation of Universal Salt Iodization, the residents’ iodine status has been qualitatively improved. However, goiter still is a problem in public health. Many evidences indicated that goiter might have malignant potency and could develop to carcinoma. The patients with goiter suffered a significant higher risk of thyroid cancer than the control population. Prevention on goiter could effectively decrease the risk of thyroid cancer. It would benefit for the early prevention of the disease. Applicant found the Pax8 play a important role in the development of goiter, and successfully induced the Pax8 cre-loxp animal model in the previous work. In this project, applicant plan to investigate the differential expression genes in goiter by single-cell sequencing technology, study the inherited characters of goiter with different iodine intake levels, analyze the related genes to the goiter’s malignant transformation and the potential mechanisms. This program is hopeful to illustrate the inherited mechanism for goiter, and understand the relationship between goiter and thyroid carcinoma. Moreover, it is valuable for the further research on the development of thyroid cancer induced by iodine malnutrition. The results will promote the prevention and control for thyroid diseases.