单细胞转录组学分析揭示了腮腺多形性腺瘤的起源和肿瘤内异质性。
Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma.
发表日期：2023 Sep 07
作者：
Xiuyun Xu, Jiaxiang Xie, Rongsong Ling, Shengqi Ouyang, Gan Xiong, Yanwen Lu, Bokai Yun, Ming Zhang, Wenjin Wang, Xiqiang Liu, Demeng Chen, Cheng Wang
来源：
International Journal of Oral Science
摘要：
多形性腺瘤（PA）是唾液腺中最常见的良性肿瘤，形态复杂性高。然而，PA的起源和肿瘤内部异质性很大程度上尚不明确。本研究在单细胞分辨率下构建了PA的全面图谱，并显示PA展示了五个肿瘤亚群，其中三个重现了正常腮腺上皮状态，两个PA特异性上皮细胞（PASE）亚群特有于肿瘤中。然后，鉴定出了六个具有上皮细胞、骨、免疫、代谢、干性和细胞周期特征的PASE细胞亚群。此外，我们揭示了CD36+肌上皮细胞是PA中的肿瘤起始细胞（TICs），并且受PI3K-AKT通路控制。针对PI3K-AKT通路显著抑制了CD36+肌上皮细胞来源的肿瘤球和PA器官oid的生长。我们的结果对PA的多样性和起源提供了新的见解，为PA治疗中靶向PI3K-AKT信号通路提供了重要的临床意义。© 2023. 四川大学华西口腔医学院。
Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36+ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36+ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.© 2023. West China School of Stomatology Sichuan University.