Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer
Abstract Despite significant advancements in identifying novel therapeutic targets and compounds, cancer stem cells (CSCs) remain pivotal in driving therapeutic resistance and tumor progression in gastric cancer (GC). High‐resolution knowledge of the transcriptional programs underlying the role of C...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202413019 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849722730882007040 |
|---|---|
| author | Guangyu Zhang Xin Zhang Wenting Pan Xizhao Chen Lingfei Wan Chunjie Liu Yuting Yong Yue Zhao Shuli Sang Lihua Zhang Sheng Yao Yushu Guo Mingmei Wang Xinhui Wang Guangdun Peng Xinlong Yan Yanchun Wang Min Zhang |
| author_facet | Guangyu Zhang Xin Zhang Wenting Pan Xizhao Chen Lingfei Wan Chunjie Liu Yuting Yong Yue Zhao Shuli Sang Lihua Zhang Sheng Yao Yushu Guo Mingmei Wang Xinhui Wang Guangdun Peng Xinlong Yan Yanchun Wang Min Zhang |
| author_sort | Guangyu Zhang |
| collection | DOAJ |
| description | Abstract Despite significant advancements in identifying novel therapeutic targets and compounds, cancer stem cells (CSCs) remain pivotal in driving therapeutic resistance and tumor progression in gastric cancer (GC). High‐resolution knowledge of the transcriptional programs underlying the role of CSC niche in driving tumor stemness and progression is still lacking. Herein, spatial and single‐cell RNA sequencing of 32 human gastric mucosa tissues at various stages of malignancy, illuminating the phenotypic plasticity of tumor epithelium and transcriptional trajectory from mature gastric chief cells to the CSC state, which is associated with activation of EGFR and WNT signaling pathways, is conducted. Moreover, the CSCs interact with not only the immunosuppressive CXCL13+ T cells and CCL18+ M2 macrophages to evade immune surveillance, but also the inflammatory cancer‐associated fibroblasts (iCAFs) to promote tumorigenesis and maintain stemness, which construct the CSC niche leading to inferior prognosis. Notably, it is uncovered that amphiregulin (AREG) derived from iCAFs promotes tumor stemness by upregulating the expression of SOX9 in tumor cells, and contributes to drug resistance via the AREG‐ERBB2 axis. This study provides valuable insight into the characteristics of CSC niche in driving tumor stemness and progression, offering novel perspective for designing effective strategies to overcome GC therapy resistance. |
| format | Article |
| id | doaj-art-e5e7c3ce9cf04653ba5932f8032a53ed |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e5e7c3ce9cf04653ba5932f8032a53ed2025-08-20T03:11:14ZengWileyAdvanced Science2198-38442025-05-011218n/an/a10.1002/advs.202413019Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric CancerGuangyu Zhang0Xin Zhang1Wenting Pan2Xizhao Chen3Lingfei Wan4Chunjie Liu5Yuting Yong6Yue Zhao7Shuli Sang8Lihua Zhang9Sheng Yao10Yushu Guo11Mingmei Wang12Xinhui Wang13Guangdun Peng14Xinlong Yan15Yanchun Wang16Min Zhang17Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510070 ChinaDepartment of Pharmacy Medical Supplies Center Chinese PLA General Hospital Beijing 100853 ChinaBeijing International Science and Technology Cooperation Base for Antiviral Drugs Beijing Key Laboratory of Environmental and Viral Oncology College of Chemistry and Life Science Beijing University of Technology Beijing 100124 ChinaDepartment of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases First Medical Center Chinese PLA General Hospital Beijing 100853 ChinaBeijing International Science and Technology Cooperation Base for Antiviral Drugs Beijing Key Laboratory of Environmental and Viral Oncology College of Chemistry and Life Science Beijing University of Technology Beijing 100124 ChinaLaboratory of Advanced Biotechnology Beijing Institute of Biotechnology Beijing 100071 ChinaBeijing International Science and Technology Cooperation Base for Antiviral Drugs Beijing Key Laboratory of Environmental and Viral Oncology College of Chemistry and Life Science Beijing University of Technology Beijing 100124 ChinaBeijing International Science and Technology Cooperation Base for Antiviral Drugs Beijing Key Laboratory of Environmental and Viral Oncology College of Chemistry and Life Science Beijing University of Technology Beijing 100124 ChinaLaboratory of Advanced Biotechnology Beijing Institute of Biotechnology Beijing 100071 ChinaDepartment of Pathology Fourth Medical Center Chinese PLA General Hospital Beijing 100048 ChinaDepartment of General Surgery First Medical Center Chinese PLA General Hospital Beijing 100853 ChinaDepartment of Pharmacy Medical Supplies Center Chinese PLA General Hospital Beijing 100853 ChinaDepartment of Pharmacy Medical Supplies Center Chinese PLA General Hospital Beijing 100853 ChinaDepartment of Pharmacy Medical Supplies Center Chinese PLA General Hospital Beijing 100853 ChinaGuangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510070 ChinaBeijing International Science and Technology Cooperation Base for Antiviral Drugs Beijing Key Laboratory of Environmental and Viral Oncology College of Chemistry and Life Science Beijing University of Technology Beijing 100124 ChinaLaboratory of Advanced Biotechnology Beijing Institute of Biotechnology Beijing 100071 ChinaDepartment of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases First Medical Center Chinese PLA General Hospital Beijing 100853 ChinaAbstract Despite significant advancements in identifying novel therapeutic targets and compounds, cancer stem cells (CSCs) remain pivotal in driving therapeutic resistance and tumor progression in gastric cancer (GC). High‐resolution knowledge of the transcriptional programs underlying the role of CSC niche in driving tumor stemness and progression is still lacking. Herein, spatial and single‐cell RNA sequencing of 32 human gastric mucosa tissues at various stages of malignancy, illuminating the phenotypic plasticity of tumor epithelium and transcriptional trajectory from mature gastric chief cells to the CSC state, which is associated with activation of EGFR and WNT signaling pathways, is conducted. Moreover, the CSCs interact with not only the immunosuppressive CXCL13+ T cells and CCL18+ M2 macrophages to evade immune surveillance, but also the inflammatory cancer‐associated fibroblasts (iCAFs) to promote tumorigenesis and maintain stemness, which construct the CSC niche leading to inferior prognosis. Notably, it is uncovered that amphiregulin (AREG) derived from iCAFs promotes tumor stemness by upregulating the expression of SOX9 in tumor cells, and contributes to drug resistance via the AREG‐ERBB2 axis. This study provides valuable insight into the characteristics of CSC niche in driving tumor stemness and progression, offering novel perspective for designing effective strategies to overcome GC therapy resistance.https://doi.org/10.1002/advs.202413019cancer stem cells (CSCs)gastric cancer (GC)single cell RNA‐seqspatial transcriptometumor microenvironment |
| spellingShingle | Guangyu Zhang Xin Zhang Wenting Pan Xizhao Chen Lingfei Wan Chunjie Liu Yuting Yong Yue Zhao Shuli Sang Lihua Zhang Sheng Yao Yushu Guo Mingmei Wang Xinhui Wang Guangdun Peng Xinlong Yan Yanchun Wang Min Zhang Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer Advanced Science cancer stem cells (CSCs) gastric cancer (GC) single cell RNA‐seq spatial transcriptome tumor microenvironment |
| title | Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer |
| title_full | Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer |
| title_fullStr | Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer |
| title_full_unstemmed | Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer |
| title_short | Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer |
| title_sort | dissecting the spatial and single cell transcriptomic architecture of cancer stem cell niche driving tumor progression in gastric cancer |
| topic | cancer stem cells (CSCs) gastric cancer (GC) single cell RNA‐seq spatial transcriptome tumor microenvironment |
| url | https://doi.org/10.1002/advs.202413019 |
| work_keys_str_mv | AT guangyuzhang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT xinzhang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT wentingpan dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT xizhaochen dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT lingfeiwan dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT chunjieliu dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT yutingyong dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT yuezhao dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT shulisang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT lihuazhang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT shengyao dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT yushuguo dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT mingmeiwang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT xinhuiwang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT guangdunpeng dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT xinlongyan dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT yanchunwang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer AT minzhang dissectingthespatialandsinglecelltranscriptomicarchitectureofcancerstemcellnichedrivingtumorprogressioningastriccancer |