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Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma

Song Mei,  Xiaolei Wang,  Mengmeng Zhao,  Qing Huang,  Yixuan Huang,  Mingming Su,  Xinlei Zhang,  Xu Wang,  Xueyu Hao,  Tianning Wang,  Yanhua Wu,  Yuanhui Ma,  Jingnan Wang,  Peng Zhang,  Yan Zheng

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文章导航 > Journal of Genetics and Genomics  > 2025 > 优先出版
Song Mei, Xiaolei Wang, Mengmeng Zhao, Qing Huang, Yixuan Huang, Mingming Su, Xinlei Zhang, Xu Wang, Xueyu Hao, Tianning Wang, Yanhua Wu, Yuanhui Ma, Jingnan Wang, Peng Zhang, Yan Zheng. Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma[J]. 遗传学报. doi: 10.1016/j.jgg.2025.02.006
引用本文: Song Mei, Xiaolei Wang, Mengmeng Zhao, Qing Huang, Yixuan Huang, Mingming Su, Xinlei Zhang, Xu Wang, Xueyu Hao, Tianning Wang, Yanhua Wu, Yuanhui Ma, Jingnan Wang, Peng Zhang, Yan Zheng. Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma[J]. 遗传学报. doi: 10.1016/j.jgg.2025.02.006
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Song Mei, Xiaolei Wang, Mengmeng Zhao, Qing Huang, Yixuan Huang, Mingming Su, Xinlei Zhang, Xu Wang, Xueyu Hao, Tianning Wang, Yanhua Wu, Yuanhui Ma, Jingnan Wang, Peng Zhang, Yan Zheng. Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma[J]. Journal of Genetics and Genomics. doi: 10.1016/j.jgg.2025.02.006
Citation: Song Mei, Xiaolei Wang, Mengmeng Zhao, Qing Huang, Yixuan Huang, Mingming Su, Xinlei Zhang, Xu Wang, Xueyu Hao, Tianning Wang, Yanhua Wu, Yuanhui Ma, Jingnan Wang, Peng Zhang, Yan Zheng. Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma[J]. Journal of Genetics and Genomics. doi: 10.1016/j.jgg.2025.02.006
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Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma

doi: 10.1016/j.jgg.2025.02.006

  • a. Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Rare Disease Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;

  • b. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

  • c. Department of Pathology, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250100, China;

  • d. Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, China;

  • e. Department of Thoracic Surgery, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250100, China;

  • f. Beijing ClouDNA Technology Co., Ltd., Beijing 100080, China;

  • g. School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian 350122, China;

  • h. Department of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250100, China;

  • i. Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, China

基金项目: 

This study is supported by the National Natural Science Foundation of China (82002432 to J. W., 82302068 to M. Z., and 32300568 to T. W.), the Natural Science Foundation of Shandong Province (ZR2024MH159 to Y. Z., ZR2020QH179 to J. W., ZR2022QH057 to M. Z., and ZR2021QH005 to T.W.), and the China Postdoctoral Science Foundation (2024M752006 to S. M.).

详细信息
    通讯作者:

    Peng Zhang,E-mail:zhangpengdyx@163.com

    Yan Zheng,E-mail:8793822@qq.com

Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma

  • a. Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Rare Disease Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;

  • b. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

  • c. Department of Pathology, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250100, China;

  • d. Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, China;

  • e. Department of Thoracic Surgery, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250100, China;

  • f. Beijing ClouDNA Technology Co., Ltd., Beijing 100080, China;

  • g. School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian 350122, China;

  • h. Department of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250100, China;

  • i. Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, China

Funds: 

This study is supported by the National Natural Science Foundation of China (82002432 to J. W., 82302068 to M. Z., and 32300568 to T. W.), the Natural Science Foundation of Shandong Province (ZR2024MH159 to Y. Z., ZR2020QH179 to J. W., ZR2022QH057 to M. Z., and ZR2021QH005 to T.W.), and the China Postdoctoral Science Foundation (2024M752006 to S. M.).

    摘要
  • 摘要:

    Although the spatial characteristics within the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) have been identified, the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear. Using spatial transcriptomics (ST) and single-cell RNA-sequencing (scRNA-seq) data from multi-regional LUAD biopsies consisting of tumor core, tumor edge, and normal area, we sought to delineate the spatial heterogeneity and driving factors of cell colocalization. Two cancer cell sub-clusters (Cancer_c1 and Cancer_c2), associated with LUAD initiation and metastasis, respectively, exhibit distinct spatial distributions and immune cell colocalizations. In particular, Cancer_c1, enriched within the tumor core, could directly interact with B cells or indirectly recruit B cells through macrophages. Conversely, Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8+ T cells. Collectively, our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD, providing insights for developing therapeutic strategies for cancer intervention.

    Abstract:

    Although the spatial characteristics within the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) have been identified, the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear. Using spatial transcriptomics (ST) and single-cell RNA-sequencing (scRNA-seq) data from multi-regional LUAD biopsies consisting of tumor core, tumor edge, and normal area, we sought to delineate the spatial heterogeneity and driving factors of cell colocalization. Two cancer cell sub-clusters (Cancer_c1 and Cancer_c2), associated with LUAD initiation and metastasis, respectively, exhibit distinct spatial distributions and immune cell colocalizations. In particular, Cancer_c1, enriched within the tumor core, could directly interact with B cells or indirectly recruit B cells through macrophages. Conversely, Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8+ T cells. Collectively, our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD, providing insights for developing therapeutic strategies for cancer intervention.

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出版历程
  • 收稿日期:  2025-01-18
  • 录用日期:  2025-02-14
  • 修回日期:  2025-02-12
  • 网络出版日期:  2025-07-11

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