Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation
Abstract Breast cancers present intricate microenvironments comprising heterotypic cellular interactions, yet a comprehensive spatial map remained to be established. Here, we employed the DNA nanoball-based genome-wide in situ sequencing (Stereo-seq) to visualize the geospatial architecture of 30 pr...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58511-0 |
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| author | Xin Wang Zhanyu Wang Qijun Liao Pei Yuan Junpu Mei Yin Zhang Chao Wu Xiyu Kang Sufei Zheng Chenxuan Yang Jiaxiang Liu Qingyao Shang Jiangtao Li Bingning Wang Liangyu Li Hui Liu Weining Hu Zhensheng Dong Jie Zhao Linying Wang Tao Liu Yusheng Den Chengrui Wang Lijuan Han Qianjun Chen Huanming Yang Xun Xu Jie He Zhen Yue Nan Sun Xiaodong Fang Jianming Ying |
| author_facet | Xin Wang Zhanyu Wang Qijun Liao Pei Yuan Junpu Mei Yin Zhang Chao Wu Xiyu Kang Sufei Zheng Chenxuan Yang Jiaxiang Liu Qingyao Shang Jiangtao Li Bingning Wang Liangyu Li Hui Liu Weining Hu Zhensheng Dong Jie Zhao Linying Wang Tao Liu Yusheng Den Chengrui Wang Lijuan Han Qianjun Chen Huanming Yang Xun Xu Jie He Zhen Yue Nan Sun Xiaodong Fang Jianming Ying |
| author_sort | Xin Wang |
| collection | DOAJ |
| description | Abstract Breast cancers present intricate microenvironments comprising heterotypic cellular interactions, yet a comprehensive spatial map remained to be established. Here, we employed the DNA nanoball-based genome-wide in situ sequencing (Stereo-seq) to visualize the geospatial architecture of 30 primary breast tumors and metastatic lymph nodes across different molecular subtypes. This unprecedented high-resolution atlas unveils the fine structure of the tumor vasculature, highlighting heterogeneity in phenotype, spatial distribution, and intercellular communication within both endothelial and perivascular cells. In particular, venular smooth muscle cells are identified as the primary source of CCL21/CCL19 within the microenvironment. In collaboration with ACKR1-positive endothelial cells, they create a chemokine-rich venular niche to synergistically promote lymphocyte extravasation into tumors. High venule density predicts increased immune infiltration and improved clinical outcomes. This study provides a detailed spatial landscape of human breast cancer, offering key insights into the venular regulation of tumor immune infiltration. |
| format | Article |
| id | doaj-art-45a7a82fff974dc6ba9a7d088e2e01a6 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-45a7a82fff974dc6ba9a7d088e2e01a62025-08-20T03:06:54ZengNature PortfolioNature Communications2041-17232025-04-0116111810.1038/s41467-025-58511-0Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasationXin Wang0Zhanyu Wang1Qijun Liao2Pei Yuan3Junpu Mei4Yin Zhang5Chao Wu6Xiyu Kang7Sufei Zheng8Chenxuan Yang9Jiaxiang Liu10Qingyao Shang11Jiangtao Li12Bingning Wang13Liangyu Li14Hui Liu15Weining Hu16Zhensheng Dong17Jie Zhao18Linying Wang19Tao Liu20Yusheng Den21Chengrui Wang22Lijuan Han23Qianjun Chen24Huanming Yang25Xun Xu26Jie He27Zhen Yue28Nan Sun29Xiaodong Fang30Jianming Ying31Department of Breast Surgical Oncology, 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 CollegeBGI ResearchDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBGI ResearchBGI ResearchBGI ResearchDepartment of Breast Surgical Oncology, 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 Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Breast Surgical Oncology, 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 Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchBGI ResearchState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineBGI ResearchBGI ResearchDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBGI ResearchDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBGI ResearchState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Breast cancers present intricate microenvironments comprising heterotypic cellular interactions, yet a comprehensive spatial map remained to be established. Here, we employed the DNA nanoball-based genome-wide in situ sequencing (Stereo-seq) to visualize the geospatial architecture of 30 primary breast tumors and metastatic lymph nodes across different molecular subtypes. This unprecedented high-resolution atlas unveils the fine structure of the tumor vasculature, highlighting heterogeneity in phenotype, spatial distribution, and intercellular communication within both endothelial and perivascular cells. In particular, venular smooth muscle cells are identified as the primary source of CCL21/CCL19 within the microenvironment. In collaboration with ACKR1-positive endothelial cells, they create a chemokine-rich venular niche to synergistically promote lymphocyte extravasation into tumors. High venule density predicts increased immune infiltration and improved clinical outcomes. This study provides a detailed spatial landscape of human breast cancer, offering key insights into the venular regulation of tumor immune infiltration.https://doi.org/10.1038/s41467-025-58511-0 |
| spellingShingle | Xin Wang Zhanyu Wang Qijun Liao Pei Yuan Junpu Mei Yin Zhang Chao Wu Xiyu Kang Sufei Zheng Chenxuan Yang Jiaxiang Liu Qingyao Shang Jiangtao Li Bingning Wang Liangyu Li Hui Liu Weining Hu Zhensheng Dong Jie Zhao Linying Wang Tao Liu Yusheng Den Chengrui Wang Lijuan Han Qianjun Chen Huanming Yang Xun Xu Jie He Zhen Yue Nan Sun Xiaodong Fang Jianming Ying Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation Nature Communications |
| title | Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation |
| title_full | Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation |
| title_fullStr | Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation |
| title_full_unstemmed | Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation |
| title_short | Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation |
| title_sort | spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation |
| url | https://doi.org/10.1038/s41467-025-58511-0 |
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