Related Experiment Video
Updated: Jan 13, 2026
Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
Published on: March 21, 2021
Single-cell landscape of mouse lungs exposed to intermittent hypoxia
Pengdou Zheng1,2, Lingling Wang1, Xiaoyan Zhu1
1Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, National Health Commission (NHC), Huazhong University of Science and Technology, Wuhan, 430030, China.
Background:
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a prevalent respiratory disorder characterized by intermittent hypoxia (IH), which promotes pulmonary complications. However, the cellular and molecular mechanisms underlying IH-induced lung remodeling remain poorly understood.
Methods:
We performed comprehensive single-cell RNA sequencing (scRNA-seq) analysis of lung tissue from IH-exposed mice (GSE145435). Computational approaches were used to characterize cellular heterogeneity, transcriptional programs, and cell-cell interactions. Key findings were validated using intervention studies with the SP1 inhibitor plicamycin.
Results:
Our analysis revealed the following: IH induced: (1) the expansion of four distinct fibroblast subsets; (2) polarization of proinflammatory Mφ1 (IL-18 high) with activated PPAR signaling; (3) altered T-cell dynamics featuring CD4⁺ T-cell accumulation and reduced memory T cells; (4) endothelial remodeling (endo2 subtype dominance) mediated by Ccl6-Ccr2 interactions. Moreover, SP1 inhibition attenuated IH-induced pathology, reducing collagen deposition and inflammatory markers.
Conclusions:
This study identifies SP1 as a master regulator of IH-induced pulmonary remodeling through coordinated control of fibrotic, inflammatory, and vascular pathways. These findings provide mechanistic insights into OSAHS-related complications and highlight SP1 inhibition as a potential therapeutic strategy for hypoxia-induced lung injury.
