Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics

Abstract

Mononuclear phagocytes are organized in a complex system of ontogenetically and functionally distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic, and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections. We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover, we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey.

Broncho Alveolar Dendritic Cells and Macrophages Are Highly Similar to Their Interstitial Counterparts

“…The BAL cells were then sorted by flow cytometry and the transcriptomic expressions of 10 genes previously identified as differentially expressed in these populations by us [2, 14] and others [4, 15, 16] were measured by RT-qPCR (Fig 2A). In order to easily compare those results with those we previously obtained, we depicted previously published data from parenchymal cells [2] as closed symbols in Fig 2A and as the “PAR” columns in the heat map (Fig 2B) we designed to summarize the RT-qPCR data.…”

CD1− and CD1+ porcine blood dendritic cells are enriched for the orthologues of the two major mammalian conventional subsets

“…That these subpopulations of cDC share a common genetic signature has been reported previously in sheep, mouse and human243350556465. A recent study confirmed orthology between the blood cDC1 population in pig with mouse and human equivalents, although the authors were unable to make any claims on the cDC2 population56. In this study, cDC1 were identified based on CADM1 expression27 rather than an absence of CD1 expression as employed here.…”

“…To explore a broader range of DC markers, we compared the porcine DC populations at the transcriptome level. This also enabled us to determine if the DC populations share a common gene expression signature as has been recently described for other species2433505556. Employing a custom made NimbleGen 12 × 135 K porcine array spanning a total of 19,351 genes, we investigated the gene expression profile of the FACS sorted CD1 − , CD1 + and pDC populations from three separate pigs and compared these with monocytes from the same pigs.…”

A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

“…In addition, the pattern of CD11c expression on pig skin and blood myeloid cell subsets whose organization aligns across species (41–43), is closer to the human than to the mouse one, making pig a pertinent preclinical model to evaluate this type of targeting. Indeed, CD11c shows a higher expression on cDC2 than on cDC1 and is highly expressed on skin monocyte-derived cells in the pig and human (25, 44) and not in the mouse (45).…”