Cellular and molecular mechanisms of fibrosis and resolution in bleomycin-induced pulmonary fibrosis mouse model revealed by spatial transcriptome analysis
Qingsong Li,
Yue Wang,
Liu Ji,
Jianhan He,
Haixia Liu,
Weizhen Xue,
Huihui Yue,
Ruihan Dong,
Xin Liu,
Daqing Wang,
Huilan Zhang
Affiliations
Qingsong Li
BGI-Beijing, Beijing 102601, China
Yue Wang
BGI-Beijing, Beijing 102601, China
Liu Ji
Dalian Maternal and Child Health Hospital of Liaoning Province, Dalian 116033, China
Jianhan He
Department of Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
Haixia Liu
BGI-Beijing, Beijing 102601, China
Weizhen Xue
BGI-Beijing, Beijing 102601, China
Huihui Yue
Department of Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
Ruihan Dong
Department of Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China
Dalian Maternal and Child Health Hospital of Liaoning Province, Dalian 116033, China; Corresponding author.
Huilan Zhang
Department of Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China; Corresponding author.
The bleomycin-induced pulmonary fibrosis mouse model is commonly used in idiopathic pulmonary fibrosis research, but its cellular and molecular changes and efficiency as a model at the molecular level are not fully understood. In this study, we used spatial transcriptome technology to investigate the cellular and molecular changes in the lungs of bleomycin-induced pulmonary fibrosis mouse models. Our analyses revealed cell dynamics during fibrosis in epithelial cells, mesenchymal cells, immunocytes, and erythrocytes with their spatial distribution available. We confirmed the differentiation of the alveolar type II (AT2) cell type expressing Krt8, and we inferred their trajectories from both the AT2 cells and club cells. In addition to the fibrosis process, we also noticed evidence of self-resolving, especially to identify possible self-resolving related genes, including Prkca. Our findings provide insights into the cellular and molecular mechanisms underlying fibrosis resolution and represent the first spatiotemporal transcriptome dataset of the bleomycin-induced fibrosis mouse model.