Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-09-07 DOI:10.1038/s41368-023-00243-2
Xiuyun Xu, Jiaxiang Xie, Rongsong Ling, Shengqi Ouyang, Gan Xiong, Yanwen Lu, Bokai Yun, Ming Zhang, Wenjin Wang, Xiqiang Liu, Demeng Chen, Cheng Wang
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引用次数: 1

Abstract

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.

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单细胞转录组学分析揭示了腮腺多形性腺瘤的起源和瘤内异质性。
多形性腺瘤(PA)是唾液腺中最常见的良性肿瘤,具有高度的形态复杂性。然而,PA的起源和肿瘤内异质性在很大程度上是未知的。在这里,我们在单细胞分辨率下构建了PA的综合图谱,并显示PA表现出五个肿瘤亚群,三个再现正常腮腺的上皮状态,以及两个肿瘤特有的PA特异性上皮细胞(PASE)群体。然后,鉴定出6个PASE细胞亚群,它们在上皮、骨、免疫、代谢、干性和细胞周期特征上存在差异。此外,我们发现CD36+肌上皮细胞是PA的肿瘤启动细胞(tic),并由PI3K-AKT通路主导。靶向PI3K-AKT通路可显著抑制CD36+肌上皮细胞衍生的肿瘤球和PA类器官的生长。我们的研究结果为PA的多样性和起源提供了新的见解,为靶向PI3K-AKT信号通路治疗PA提供了重要的临床意义。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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