Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer
Abstract Background Gastric cancer is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are a key component of the TME, exhibit significant heterogeneity and play crucial roles in tumor progression. Therefore, a compre...
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2025-03-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06376-8 |
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| author | Xijie Zhang Bo Ren Bo Liu Rui Wang Sen Li Yuzhou Zhao Wence Zhou |
| author_facet | Xijie Zhang Bo Ren Bo Liu Rui Wang Sen Li Yuzhou Zhao Wence Zhou |
| author_sort | Xijie Zhang |
| collection | DOAJ |
| description | Abstract Background Gastric cancer is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are a key component of the TME, exhibit significant heterogeneity and play crucial roles in tumor progression. Therefore, a comprehensive understanding of CAFs is essential for developing novel therapeutic strategies for gastric cancer. Methods This study investigates the characteristics and functional information of CAF subtypes and explores the intercellular communication between CAFs and malignant epithelial cells (ECs) in gastric cancer by analyzing single-cell sequencing data from 24 gastric cancer samples. CellChat was employed to map intercellular communication, and Seurat was used to integrate single-cell sequencing data with spatial transcriptome data to reconstruct a comprehensive single-cell spatial map. The spatial relationship between apCAFs and cancer cells was analyzed using multicolor immunohistochemistry. Results Cells were categorized into nine distinct categories, revealing a positive correlation between the proportions of epithelial cells (ECs) and fibroblasts. Furthermore, six fibroblast subpopulations were identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle cells (SMCs), and proliferative CAFs (pCAFs). Each of these subpopulations was linked to various biological processes and immune responses. Malignant ECs exhibited heightened intercellular communication, particularly with CAF subpopulations, through specific ligand-receptor interactions. High-density regions of CAF subpopulations displayed spatial exclusivity, with pericytes serving as a source for iCAFs, mCAFs, and apCAFs. Notably, malignant ECs and apCAFs showed increased interactions, with certain ligand-receptor pairs potentially impacting the prognosis of gastric cancer. Multiplex immunohistochemistry (mIHC) confirmed the close spatial proximity of apCAFs to cancer cells in gastric cancer. Conclusion Our study provided a comprehensive characterization of CAF heterogeneity in gastric cancer and revealed the intricate intercellular networks within the TME. The identified CAF subpopulations and their interactions with malignant cells could serve as potential therapeutic targets. |
| format | Article |
| id | doaj-art-a1fa4af80be7407b82b0934ee304ff1c |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-a1fa4af80be7407b82b0934ee304ff1c2025-08-20T02:41:34ZengBMCJournal of Translational Medicine1479-58762025-03-0123111410.1186/s12967-025-06376-8Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancerXijie Zhang0Bo Ren1Bo Liu2Rui Wang3Sen Li4Yuzhou Zhao5Wence Zhou6The Second Clinical Medical School, Lanzhou UniversityThe Second Clinical Medical School, Lanzhou UniversityThe Second Clinical Medical School, Lanzhou UniversityThe Second Clinical Medical School, Lanzhou UniversityDepartment of General Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of General Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalThe Second Clinical Medical School, Lanzhou UniversityAbstract Background Gastric cancer is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are a key component of the TME, exhibit significant heterogeneity and play crucial roles in tumor progression. Therefore, a comprehensive understanding of CAFs is essential for developing novel therapeutic strategies for gastric cancer. Methods This study investigates the characteristics and functional information of CAF subtypes and explores the intercellular communication between CAFs and malignant epithelial cells (ECs) in gastric cancer by analyzing single-cell sequencing data from 24 gastric cancer samples. CellChat was employed to map intercellular communication, and Seurat was used to integrate single-cell sequencing data with spatial transcriptome data to reconstruct a comprehensive single-cell spatial map. The spatial relationship between apCAFs and cancer cells was analyzed using multicolor immunohistochemistry. Results Cells were categorized into nine distinct categories, revealing a positive correlation between the proportions of epithelial cells (ECs) and fibroblasts. Furthermore, six fibroblast subpopulations were identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle cells (SMCs), and proliferative CAFs (pCAFs). Each of these subpopulations was linked to various biological processes and immune responses. Malignant ECs exhibited heightened intercellular communication, particularly with CAF subpopulations, through specific ligand-receptor interactions. High-density regions of CAF subpopulations displayed spatial exclusivity, with pericytes serving as a source for iCAFs, mCAFs, and apCAFs. Notably, malignant ECs and apCAFs showed increased interactions, with certain ligand-receptor pairs potentially impacting the prognosis of gastric cancer. Multiplex immunohistochemistry (mIHC) confirmed the close spatial proximity of apCAFs to cancer cells in gastric cancer. Conclusion Our study provided a comprehensive characterization of CAF heterogeneity in gastric cancer and revealed the intricate intercellular networks within the TME. The identified CAF subpopulations and their interactions with malignant cells could serve as potential therapeutic targets.https://doi.org/10.1186/s12967-025-06376-8Gastric cancerCancer-associated fibroblastsSingle-cell transcriptomicsCell–cell interactionsTumor microenvironment |
| spellingShingle | Xijie Zhang Bo Ren Bo Liu Rui Wang Sen Li Yuzhou Zhao Wence Zhou Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer Journal of Translational Medicine Gastric cancer Cancer-associated fibroblasts Single-cell transcriptomics Cell–cell interactions Tumor microenvironment |
| title | Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer |
| title_full | Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer |
| title_fullStr | Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer |
| title_full_unstemmed | Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer |
| title_short | Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer |
| title_sort | single cell rna sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer associated fibroblasts in gastric cancer |
| topic | Gastric cancer Cancer-associated fibroblasts Single-cell transcriptomics Cell–cell interactions Tumor microenvironment |
| url | https://doi.org/10.1186/s12967-025-06376-8 |
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