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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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Single-cell landscape of mouse lungs exposed to intermittent hypoxia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月28日

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  • Pengdou Zheng,
  • Lingling Wang,
  • Xiaoyan Zhu,
  • Zhenyu Mao,
  • Fengqin Zhang,
  • Guisha Zi,
  • Lixiang Chen,
  • Huiguo Liu,
  • Ling Zhou,
  • Wei Liu

摘要

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.

Graphical Abstract