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

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

  • Int J Oral Sci. 2023 Sep 7;15(1):38. doi: 10.1038/s41368-023-00243-2.
Xiuyun Xu # 1 2 3,  Jiaxiang Xie # 1 2 3,  Rongsong Ling 4,  Shengqi Ouyang 1 2 3,  Gan Xiong 1 2 3,  Yanwen Lu 1 2 3,  Bokai Yun 1 2 3,  Ming Zhang 1 2 3,  Wenjin Wang 1 2 3,  Xiqiang Liu 5,  Demeng Chen 6,  Cheng Wang 7 8 9
Affiliations

Affiliations

  • 1 Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
  • 2 Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
  • 3 Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
  • 4 Institute for Advanced Study, Shenzhen University, Shenzhen, China.
  • 5 Department of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 6 Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. chendm29@mail.sysu.edu.cn.
  • 7 Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China. wangch75@mail.sysu.edu.cn.
  • 8 Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China. wangch75@mail.sysu.edu.cn.
  • 9 Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China. wangch75@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 37679344 DOI: 10.1038/s41368-023-00243-2
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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