Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases
Abstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC pat...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01369-x |
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| author | Wei Guo Bolun Zhou Lizhou Dou Lei Guo Yong Li Jianjun Qin Zhen Wang Qilin Huai Xuemin Xue Yin Li Jianming Ying Qi Xue Shugeng Gao Jie He |
| author_facet | Wei Guo Bolun Zhou Lizhou Dou Lei Guo Yong Li Jianjun Qin Zhen Wang Qilin Huai Xuemin Xue Yin Li Jianming Ying Qi Xue Shugeng Gao Jie He |
| author_sort | Wei Guo |
| collection | DOAJ |
| description | Abstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals. |
| format | Article |
| id | doaj-art-e24a18a637e54187b979979794a8f76c |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-e24a18a637e54187b979979794a8f76c2025-02-09T12:14:18ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-01571597110.1038/s12276-024-01369-xSingle-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastasesWei Guo0Bolun Zhou1Lizhou Dou2Lei Guo3Yong Li4Jianjun Qin5Zhen Wang6Qilin Huai7Xuemin Xue8Yin Li9Jianming Ying10Qi Xue11Shugeng Gao12Jie He13Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals.https://doi.org/10.1038/s12276-024-01369-x |
| spellingShingle | Wei Guo Bolun Zhou Lizhou Dou Lei Guo Yong Li Jianjun Qin Zhen Wang Qilin Huai Xuemin Xue Yin Li Jianming Ying Qi Xue Shugeng Gao Jie He Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases Experimental and Molecular Medicine |
| title | Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases |
| title_full | Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases |
| title_fullStr | Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases |
| title_full_unstemmed | Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases |
| title_short | Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases |
| title_sort | single cell rna sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases |
| url | https://doi.org/10.1038/s12276-024-01369-x |
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