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- Title
Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing.
- Authors
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
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.
- Subjects
RNA sequencing; MICROGLIA; CENTRAL nervous system; TRANSCRIPTOMES
- Publication
Journal of Neuroinflammation, 2023, Vol 20, Issue 1, p1
- ISSN
1742-2094
- Publication type
Article
- DOI
10.1186/s12974-023-02809-7