DataSheet_1_Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto’s Thyroiditis.pdf

Hashimoto’s thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone’s understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

桥本甲状腺炎（Hashimoto’s thyroiditis, HT）是一种自身免疫性疾病，其发病率呈持续上升趋势。尽管科研人员对该病已开展多年研究，并发现了多种蛋白的潜在生物学效应，但其具体发病机制仍未完全阐明。为深入解析桥本甲状腺炎并推动相关研究成果向临床应用转化，我们对桥本甲状腺炎患者与健康对照个体的甲状腺细针穿刺组织标本进行了质谱分析，以期进一步揭示该病的发病机制。最终在桥本甲状腺炎患者样本中共鉴定出44种差异表达蛋白，这些蛋白在细胞黏附、细胞代谢及甲状腺素合成过程中发挥关键作用。结合患者临床样本信息，我们进一步对比了桥本甲状腺炎与甲状腺乳头状癌（papillary thyroid carcinoma, PTC）样本中基因表达调控的动态变化。更为重要的是，我们构建了患者来源的桥本甲状腺炎与甲状腺乳头状癌类器官，作为一种极具潜力的新型临床前模型，用以验证上述潜在标志物。本研究数据揭示，桥本甲状腺炎类器官存在显著的趋化因子上调特征，其中包括C-C基序趋化因子配体（C-C motif chemokine ligand, CCL）2与CCL3，这两种因子在桥本甲状腺炎的发病机制中扮演核心角色。总体而言，本研究深化了学界对桥本甲状腺炎发病机制的认知，可为该病的临床治疗提供重要参考。