Respiratory research · 2025
Single-cell landscape of mouse lungs exposed to intermittent hypoxia.
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Zheng Pengdou, Wang Lingling, Zhu Xiaoyan, Mao Zhenyu, Zhang Fengqin, Zi Guisha, Chen Lixiang, Liu Huiguo, Zhou Ling, Liu Wei
Аннотация
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.
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.