Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia

Abstract

Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare. As a basis for improved understanding to enhance biomedical and agricultural research, we sought to characterize pig microglial identity at genome-wide scale and conduct inter-species comparisons. We isolated pig hippocampal tissue and microglia from frontal cortex, hippocampus, and cerebellum, as well as alveolar macrophages from the lungs and conducted RNAsequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 239 highly enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 150 genes showing significant (adjusted p < 0.01) regional variations and that cerebellar microglia were most distinct. We compared normalized gene expression for microglia from human, mice and pigs using microglia signature gene lists derived from each species and demonstrated that a core microglial marker gene signature is conserved across species, but that species-specific expression subsets also exist. Our data provide a valuable resource defining the pig microglial transcriptome signature that validates and highlights pigs as a useful large animal species bridging between rodents and humans in which to study the role of microglia during homeostasis and disease.

Rapid conversion of porcine pluripotent stem cells into macrophages with chemically defined conditions

“…In addition, we compared the transcriptional features of pPSCdMs in this manuscript with the PSCdM from EBs (PSCdM_Meek) ( 42 ), microglia ( 58 ), peripheral blood mononuclear derived macrophages (PBMCs_Chen) and porcine alveolar macrophages (PAMs_Barbara and PAMs_Ju) ( 42 , 59 ). Pearson correlation coefficient and PCA showed that the pPSCdMs was very close to the PSCdM_Meek ( Fig.…”

“…All relevant data can be found within this article and its supporting information (SRA Accession: PRJNA1037615). Porcine alveolar macrophages RNA-seq data ( 58 , 59 ) is obtained from the NCBI GEO database (GSE172284) and the NCBI GEO database (GSE145954). Microglia RNA seq data ( 58 ) is obtained from the NCBI GEO database (GSE172284).…”

“…Porcine alveolar macrophages RNA-seq data ( 58 , 59 ) is obtained from the NCBI GEO database (GSE172284) and the NCBI GEO database (GSE145954). Microglia RNA seq data ( 58 ) is obtained from the NCBI GEO database (GSE172284). Peripheral blood mononuclear cells RNA seq data is obtained from the NCBI GEO database (GSE116701).…”