Human and Mouse Transcriptome Profiling Identifies Cross-Species Homology in Pulmonary and Lymph Node Mononuclear Phagocytes

The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells (DCs). MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Although murine MPs are well characterized, their pulmonary and lymph node (LN) human homologs remain poorly understood. To address this gap, we have created a gene expression compendium across 24 distinct human and murine lung and LN MPs, along with human blood and murine spleen MPs, to serve as validation datasets. In-depth RNA sequencing identifies corresponding human-mouse MP subtypes and determines marker genes shared and divergent across species. Unexpectedly, only 13%–23% of the top 1,000 marker genes (i.e., genes not shared across species-specific MP subtypes) overlap in corresponding human-mouse MP counterparts. Lastly, CD88 in both species helps distinguish monocytes/macrophages from DCs. Our cross-species expression compendium serves as a resource for future translational studies to investigate beforehand whether pursuing specific MP subtypes or genes will prove fruitful. [Display omitted] •Transcriptional profiling defines cross-species MPs from lung, LN, blood, and spleen•13%–23% of the top 1,000 marker genes overlap in corresponding H-M MP counterparts•CD88 expression distinguishes monocytes/macrophages from DCs in both species•This study creates a resource to inform future translational studies targeting MPs Understanding the homology of mononuclear phagocytes between humans and mice is essential for translating murine studies into human medicine. Leach et al. use in-depth RNA sequencing to define highly discriminatory marker genes for 15 human and 9 mouse MPs that align cross-species homologs and define conserved and divergent marker genes.