Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing

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dc.contributor.authorYaqubi, Moein
dc.contributor.authorGroh, Adam M. R.
dc.contributor.authorDorion, Marie-France
dc.contributor.authorAfanasiev, Elia
dc.contributor.authorLuo, Julia X. X.
dc.contributor.authorHashemi, Hadi
dc.contributor.authorSinha, Sarthak
dc.contributor.authorKieran, Nicholas W.
dc.contributor.authorBlain, Manon
dc.contributor.authorCui, Qiao-Ling
dc.contributor.authorBiernaskie, Jeff
dc.contributor.authorSrour, Myriam
dc.contributor.authorDudley, Roy
dc.contributor.authorHall, Jeffery A.
dc.contributor.authorSonnen, Joshua A.
dc.contributor.authorArbour, Nathalie
dc.contributor.authorPrat, Alexandre
dc.contributor.authorStratton, Jo A.
dc.contributor.authorAntel, Jack
dc.contributor.authorHealy, Luke M.
dc.date.accessioned2023-06-04T00:03:16Z
dc.date.available2023-06-04T00:03:16Z
dc.date.issued2023-05-30
dc.date.updated2023-06-04T00:03:16Z
dc.description.abstractAbstract 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.
dc.identifier.citationJournal of Neuroinflammation. 2023 May 30;20(1):132
dc.identifier.urihttps://doi.org/10.1186/s12974-023-02809-7
dc.identifier.urihttps://hdl.handle.net/1880/116591
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/41434
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.titleAnalysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing
dc.typeJournal Article
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