Integrative single-cell RNA-seq and ATAC-seq analysis reveals the key role of inflammatory cell activation in pulmonary arterial hypertension

Background: The cellular heterogeneity and molecular complexity of pulmonary arterial hypertension (PAH) have not been fully elucidated. Methods: Here, we constructed an integrative transcriptome and chromatin accessibility atlas of PAH mice by using single-cell RNA sequencing and single-cell ATAC sequencing. Results: macrophages. Given its restricted upregulation in these two key proinflammatory cell populations, we generated S100a9 global knockout mice to investigate its role in PAH. S100a9 deletion alleviated the pulmonary arterial remodeling and right ventricular dysfunction in PAH mice. Conclusion: In conclusion, this study established a comprehensive transcriptome and chromatin accessibility atlas for PAH mice and further indicated that activation of S100a9-expressing inflammatory cell might be associated with the development of PAH. Further researches are warranted to investigate the underlying mechanisms.