Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-09-01
|
| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-023-00243-2 |
| _version_ | 1797453678503788544 |
|---|---|
| author | Xiuyun Xu Jiaxiang Xie Rongsong Ling Shengqi Ouyang Gan Xiong Yanwen Lu Bokai Yun Ming Zhang Wenjin Wang Xiqiang Liu Demeng Chen Cheng Wang |
| author_facet | Xiuyun Xu Jiaxiang Xie Rongsong Ling Shengqi Ouyang Gan Xiong Yanwen Lu Bokai Yun Ming Zhang Wenjin Wang Xiqiang Liu Demeng Chen Cheng Wang |
| author_sort | Xiuyun Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:26:00Z |
| format | Article |
| id | doaj.art-1291282f986544d4a8e111d4813ce599 |
| institution | Directory Open Access Journal |
| issn | 2049-3169 |
| language | English |
| last_indexed | 2024-03-09T15:26:00Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-1291282f986544d4a8e111d4813ce5992023-11-26T12:31:29ZengNature Publishing GroupInternational Journal of Oral Science2049-31692023-09-0115111310.1038/s41368-023-00243-2Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenomaXiuyun Xu0Jiaxiang Xie1Rongsong Ling2Shengqi Ouyang3Gan Xiong4Yanwen Lu5Bokai Yun6Ming Zhang7Wenjin Wang8Xiqiang Liu9Demeng Chen10Cheng Wang11Hospital of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityInstitute for Advanced Study, Shenzhen UniversityHospital of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityDepartment of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical UniversityCenter for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityHospital of Stomatology, Sun Yat-sen UniversityAbstract 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.https://doi.org/10.1038/s41368-023-00243-2 |
| spellingShingle | Xiuyun Xu Jiaxiang Xie Rongsong Ling Shengqi Ouyang Gan Xiong Yanwen Lu Bokai Yun Ming Zhang Wenjin Wang Xiqiang Liu Demeng Chen Cheng Wang Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma International Journal of Oral Science |
| title | Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma |
| title_full | Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma |
| title_fullStr | Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma |
| title_full_unstemmed | Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma |
| title_short | Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma |
| title_sort | single cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma |
| url | https://doi.org/10.1038/s41368-023-00243-2 |
| work_keys_str_mv | AT xiuyunxu singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT jiaxiangxie singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT rongsongling singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT shengqiouyang singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT ganxiong singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT yanwenlu singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT bokaiyun singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT mingzhang singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT wenjinwang singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT xiqiangliu singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT demengchen singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma AT chengwang singlecelltranscriptomicanalysisuncoverstheoriginandintratumoralheterogeneityofparotidpleomorphicadenoma |