GSE132911
Human and murine transcriptome profiling identifies cross-species homology in pulmonary mononuclear phagocytes [DCs and Monocytes]
The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells. MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Though murine MPs are well characterized, their human homologues remain poorly understood, particularly in the lung and draining lymph nodes (LNs). Understanding these homologies, and their similarities and differences with murine MPs, is critical for identifying human genetic targets and thus developing human immunotherapies. To address this gap, we performed transcriptome-based alignment across fifteen distinct human and nine distinct murine lung and LN MPs. As controls to validate the analytical quality of cross-species pulmonary MP analysis, human blood and murine spleen MPs were used. Constrained canonical correlation, t-SNE and catplot visualization was used to align human and mouse MPs and identify MP subtypes with maximal correspondence across species. Among the top marker genes expressed in corresponding human-mouse MP pairs, only 30-10% of the genes overlapped, indicating a need for caution when identifying human gene variants and functions from mice. For instance, SPP1 is highly expressed in human interstitial macrophages but not alveolar macrophages (AMs), whereas in mice SSP1 is only expressed in AMs. Moreover, human LN dendritic cells (DCs) align best with murine LN DCs but not murine splenic DCs indicating cross-species similarity in tissue. Lastly, in both species, CD88 was the most useful cell surface marker for distinguishing monocyte/macrophages from DCs. Overall, these data provide a reference for analyzing cross-species transcriptome data and evaluating whether specific murine genes are suitable guides to identify the functionality of human MPs, or conversely, whether pursuing specific human genes in mice, is likely to be a valid and fruitful approach.  Overall design: RNA-sequencing of mouse mononuclear phagocytes from lung-draining lymph nodes and spleen.