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Defining the pig microglial transcriptome reveals their core signature, regional heterogeneity, and similarity with humans

View ORCID ProfileBarbara B Shih, Sarah M Brown, Lucas Lefevre, View ORCID ProfileNeil A Mabbott, Josef Priller, Gerard Thompson, View ORCID ProfileAlistair B Lawrence, View ORCID ProfileBarry W McColl
doi: https://doi.org/10.1101/2021.08.11.454467
Barbara B Shih
1The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
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  • ORCID record for Barbara B Shih
Sarah M Brown
1The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
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Lucas Lefevre
2UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK
3Centre for Discovery Brain Sciences, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
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Neil A Mabbott
1The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
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Josef Priller
2UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK
4Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
5Charité – Universitätsmedizin Berlin and DZNE, Charitéplatz 1, 10117 Berlin, Germany
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Gerard Thompson
3Centre for Discovery Brain Sciences, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
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Alistair B Lawrence
1The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
6Scotland’s Rural College (SRUC), West Mains Road, Edinburgh EH9 3RG
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  • For correspondence: alistair.lawrence@sruc.ac.uk
Barry W McColl
2UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK
3Centre for Discovery Brain Sciences, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
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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 characterise 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 RNA-sequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 365 highly-enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 215 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. Importantly, pig and human microglia shared greater similarity than pig and murine microglia.

Our data provide a valuable resource defining the pig microglial transcriptome signature that 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.

Main Points

  • - Defined a pig microglial transcriptome signature comprising 365 genes.

  • - Demonstrated regional variance in the pig microglial transcriptome across the brain.

  • - Revealed greater similarity between pig and human microglia than mouse.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Defining the pig microglial transcriptome reveals their core signature, regional heterogeneity, and similarity with humans
Barbara B Shih, Sarah M Brown, Lucas Lefevre, Neil A Mabbott, Josef Priller, Gerard Thompson, Alistair B Lawrence, Barry W McColl
bioRxiv 2021.08.11.454467; doi: https://doi.org/10.1101/2021.08.11.454467
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Defining the pig microglial transcriptome reveals their core signature, regional heterogeneity, and similarity with humans
Barbara B Shih, Sarah M Brown, Lucas Lefevre, Neil A Mabbott, Josef Priller, Gerard Thompson, Alistair B Lawrence, Barry W McColl
bioRxiv 2021.08.11.454467; doi: https://doi.org/10.1101/2021.08.11.454467

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