Deconvoluting sex-dependent dendritic cell-monocyte lineages in emphysematous lung tissue with bulk and single-cell RNA sequencing

Abstract Emphysema is a unique type of chronic obstructive pulmonary disease, and sex may influence susceptibility. After cigarette smoke exposure, murine males and ovariectomized females developed more severe emphysema. Herein, we present divergent bulk and single-cell transcriptomic profiles between male and female murine lungs. Weighted Gene Co-Expression Network Analysis of the bulk lung RNA sequencing identified a Green gene module that correlated with male sex and ovariectomy. The Green gene module was enriched in common monocyte progenitors, classical monocytes, type 1 dendritic cells, and macrophages from 83,698 murine cells exposed to air or cigarette smoke for five months. Sexual dimorphism altered the compositions and transcriptome of the clusters enriched with the Green gene module. This comprehensive transcriptomic analysis advances our understanding of dynamic cellular responses controlled by sexual dimorphism during the development of emphysematous pulmonary tissue remodeling and reveals potential targets for mechanistic studies in the future.