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. Though murine MPs are well-characterized, their pulmonary and lymph node (LN) human homologs remain poorly understood. To address this gap, we created a gene expression compendium across 15-distinct human and 9-distinct murine MPs from lung, LN, blood, and spleen with the latter two as controls since they are the best defined human-mouse MP homologs. In-depth RNA sequencing identified corresponding human-mouse MP subtypes and determined marker genes shared or not between species counterparts. Unexpectedly, at the gene expression level, only 13-23% of the top 1000 marker genes overlapped in corresponding human-mouse MP counterparts, indicating a need for caution when translating mouse studies to human gene targets and functions. Lastly, CD88 was useful in both species to distinguish macrophage/monocytes from DCs. Our cross-species expression compendium serves as a resource for future translational studies to investigate beforehand whether pursuing specific MP subtypes, or gene will prove fruitful.