ORIGINAL RESEARCH article

Front. Immunol.

Sec. Molecular Innate Immunity

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1609616

Single-Cell and Spatial Transcriptomics Reveal a Stress-Induced EMT-like Epithelial Subset Driving Immune Activation in Silica-Injured Lung

Provisionally accepted
Tao WangTao Wang1,2,3Jianfeng HaoJianfeng Hao1,2,3BING LIBING LI2,3Ahjol HyrahtAhjol Hyraht4Jialing WangJialing Wang2,3Henglei XiaHenglei Xia2,3Qingbin WuQingbin Wu1Wei GaoWei Gao1Congxia ChenCongxia Chen1Chuanqing YuChuanqing Yu1Xiuqun GongXiuqun Gong1Ting LiTing Li5Mei ZhangMei Zhang1,2,3Yinghai XieYinghai Xie1*Xinrong TaoXinrong Tao1,2,3*
  • 1Department of Neurology, The First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital ), Huainan 232001, China；, Huainan, China
  • 2School of Public Health, Anhui University of Science and Technology, Huainan, Anhui Province, China
  • 3School of Medicine, Anhui University of Science and Technology, Huainan, Anhui Province, China
  • 4Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China
  • 5Kunshan Integrated Traditional Chinese and Western Medicine Hospital,Kunshan 215300,Jiangsu,China, Kunshan, China

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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 epithelialmesenchymal 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.

Keywords: Silicosis, Alveolar epithelial cells, single-cell RNA sequencing, Spatial transcriptomics, Epithelial-immune crosstalk

Received: 11 Apr 2025; Accepted: 19 May 2025.

Copyright: © 2025 Wang, Hao, LI, Hyraht, Wang, Xia, Wu, Gao, Chen, Yu, Gong, Li, Zhang, Xie and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yinghai Xie, Department of Neurology, The First Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital ), Huainan 232001, China；, Huainan, China
Xinrong Tao, School of Public Health, Anhui University of Science and Technology, Huainan, Anhui Province, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material