Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung
The mechanism that lung epithelial cells regulate immune responses during chronic injury still remains unclear. Here, we combined single-cell RNA sequencing with spatial transcriptomics to track epithelial dynamics in silica (SiO2)-exposed mouse lungs. By day 56, SiO2 induced significant epithelial...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609616/full |
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| author | Tao Wang Tao Wang Tao Wang Jianfeng Hao Bing Li Bing Li Ahjol Hyraht Jialing Wang Jialing Wang Henglei Xia Qingbin Wu Wei Gao Congxia Chen Chuanqing Yu Xiuqun Gong Ting Li Mei Zhang Mei Zhang Mei Zhang Yinghai Xie Xinrong Tao Xinrong Tao Xinrong Tao |
| author_facet | Tao Wang Tao Wang Tao Wang Jianfeng Hao Bing Li Bing Li Ahjol Hyraht Jialing Wang Jialing Wang Henglei Xia Qingbin Wu Wei Gao Congxia Chen Chuanqing Yu Xiuqun Gong Ting Li Mei Zhang Mei Zhang Mei Zhang Yinghai Xie Xinrong Tao Xinrong Tao Xinrong Tao |
| author_sort | Tao Wang |
| collection | DOAJ |
| description | The mechanism that lung epithelial cells regulate immune responses during chronic injury still remains unclear. Here, we combined single-cell RNA sequencing with spatial transcriptomics to track epithelial dynamics in silica (SiO2)-exposed mouse lungs. By day 56, SiO2 induced significant epithelial proliferation, followed with a distinct C0 subset emerging as the dominant population. C0 cells co-expressed surfactant genes (Sftpc, Scgb3a2), mesenchymal markers (Vim, Mmp12), and pro-inflammatory cytokines (Ccl6, S100a8/a9), reflecting a hybrid phenotype. Spatial and cell-cell interaction analyses showed C0 cells engaging macrophages and neutrophils through SPP1-CD44, APP-CD74, and GRN-MARCO signaling, driving immune recruitment and activation. Pseudotime and CytoTRACE analyses indicated that C0 cells represent a late-stage, low-stemness state with epithelial-mesenchymal transition (EMT)-like features. Taken together, these findings reveal a novel, stress-induced epithelial subset that amplifies immune crosstalk and tissue remodeling, offering new perspectives on silica-induced lung injury. |
| format | Article |
| id | doaj-art-a98ecd5adb01465e8e26ab3e2e1650ec |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a98ecd5adb01465e8e26ab3e2e1650ec2025-08-20T09:43:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16096161609616Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lungTao Wang0Tao Wang1Tao Wang2Jianfeng Hao3Bing Li4Bing Li5Ahjol Hyraht6Jialing Wang7Jialing Wang8Henglei Xia9Qingbin Wu10Wei Gao11Congxia Chen12Chuanqing Yu13Xiuqun Gong14Ting Li15Mei Zhang16Mei Zhang17Mei Zhang18Yinghai Xie19Xinrong Tao20Xinrong Tao21Xinrong Tao22The First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, ChinaSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, ChinaSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, ChinaSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, ChinaSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaKunshan Integrated Traditional Chinese and Western Medicine Hospital, Kunshan, Jiangsu, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, ChinaSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaThe First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, ChinaSchool of Public Health, Anhui University of Science and Technology, Hefei, Anhui, ChinaSchool of Medicine, Anhui University of Science and Technology, Huainan, Anhui, ChinaThe mechanism that lung epithelial cells regulate immune responses during chronic injury still remains unclear. Here, we combined single-cell RNA sequencing with spatial transcriptomics to track epithelial dynamics in silica (SiO2)-exposed mouse lungs. By day 56, SiO2 induced significant epithelial proliferation, followed with a distinct C0 subset emerging as the dominant population. C0 cells co-expressed surfactant genes (Sftpc, Scgb3a2), mesenchymal markers (Vim, Mmp12), and pro-inflammatory cytokines (Ccl6, S100a8/a9), reflecting a hybrid phenotype. Spatial and cell-cell interaction analyses showed C0 cells engaging macrophages and neutrophils through SPP1-CD44, APP-CD74, and GRN-MARCO signaling, driving immune recruitment and activation. Pseudotime and CytoTRACE analyses indicated that C0 cells represent a late-stage, low-stemness state with epithelial-mesenchymal transition (EMT)-like features. Taken together, these findings reveal a novel, stress-induced epithelial subset that amplifies immune crosstalk and tissue remodeling, offering new perspectives on silica-induced lung injury.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609616/fullsilicosisalveolar epithelial cellssingle-cell RNA sequencingspatial transcriptomicsepithelial-immune crosstalk |
| spellingShingle | Tao Wang Tao Wang Tao Wang Jianfeng Hao Bing Li Bing Li Ahjol Hyraht Jialing Wang Jialing Wang Henglei Xia Qingbin Wu Wei Gao Congxia Chen Chuanqing Yu Xiuqun Gong Ting Li Mei Zhang Mei Zhang Mei Zhang Yinghai Xie Xinrong Tao Xinrong Tao Xinrong Tao Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung Frontiers in Immunology silicosis alveolar epithelial cells single-cell RNA sequencing spatial transcriptomics epithelial-immune crosstalk |
| title | Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung |
| title_full | Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung |
| title_fullStr | Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung |
| title_full_unstemmed | Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung |
| title_short | Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung |
| title_sort | single cell and spatial transcriptomics reveal a stress induced emt like epithelial subset driving immune activation in silica injured lung |
| topic | silicosis alveolar epithelial cells single-cell RNA sequencing spatial transcriptomics epithelial-immune crosstalk |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609616/full |
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