Abstract
SUMMARYThe 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.
Highlights
Mice are the most commonly used organisms to study human diseases; they breed rapidly and can be genetically modified, accelerating the pace of discovery
Ten different mononuclear phagocyte (MP) populations were sorted from each lung donor, and 5 different populations were sorted from each blood donor (Figure 1A and Figure S1)
Putative MP subtype labels were assigned based on 1) analyses of over 100 human lungs examined in our laboratory for given MP populations consistently observed regardless of age and gender and 2) well-established cell surface markers considered to selectively identify macrophages or dendritic cells (DCs) (Figures 1A, 1C, S1) (Gibbings and Jakubzick, 2018b, Gibbings and Jakubzick, 2018a, Desch et al, 2015, Bharat et al, 2015, Misharin et al, 2013, Yu et al, 2015, Yu and Tighe, 2018, Guilliams et al, 2016, Bharat et al, 2016)
Summary
Mice are the most commonly used organisms to study human diseases; they breed rapidly and can be genetically modified, accelerating the pace of discovery. A Nobel prize-winning discovery, were first observed in the immune system of mice and translated for therapeutic use in humans (Altmann, 2018); and the development of GM-CSF therapy for pulmonary alveolar proteinosis (PAP) was influenced by observations in mice, where the deficiency of GM-CSF results in PAP (Trapnell et al, 2009). In spite of these encouraging translational examples, numerous failures in drug development across multiple diseases make it clear that rodent-to-human translation remains an important challenge (Begley and Ellis, 2012). Assessing the transcriptome alignment of cross-species human-mouse MPs is crucial
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