Author:
Yaqubi Moein,Groh Adam M. R.,Dorion Marie-France,Afanasiev Elia,Luo Julia Xiao Xuan,Hashemi Hadi,Sinha Sarthak,Kieran Nicholas W.,Blain Manon,Cui Qiao-Ling,Biernaskie Jeff,Srour Myriam,Dudley Roy,Hall Jeffery A.,Sonnen Joshua A.,Arbour Nathalie,Prat Alexandre,Stratton Jo Anne,Antel Jack,Healy Luke M.
Abstract
Abstract
Background
Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.
Method
In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope.
Results
We showed that pre-natal microglia have a distinct transcriptional and regulatory signature relative to their post-natal counterparts that includes an upregulation of phagocytic pathways. We confirmed upregulation of CD36, a positive regulator of phagocytosis, in pre-natal samples compared to adult samples in situ. Moreover, we showed adult microglia have more pro-inflammatory signature compared to microglia from other developmental ages. We indicated that adult microglia are more immune responsive by secreting increased levels of pro-inflammatory cytokines in response to LPS treatment compared to the pre-natal microglia. We further validated in situ up-regulation of IL18 and CXCR4 in human adult brain section compared to the pre-natal brain section. Finally, trajectory analysis indicated that the transcriptional signatures adopted by microglia throughout development are in response to a changing brain microenvironment and do not reflect predetermined developmental states.
Conclusion
In all, this study provides unique insight into the development of human microglia and a useful reference for understanding microglial contribution to developmental and age-related human disease.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Cited by
6 articles.
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