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

Journal of Neuroinflammation

Research

Sarthak Sinha¹  Jeff Biernaskie¹  Hadi Hashemi²  Julia Xiao Xuan Luo³  Alexandre Prat⁴  Joshua A. Sonnen⁵  Nathalie Arbour⁶  Marie-France Dorion⁷  Manon Blain⁷  Jo Anne Stratton⁷  Adam M. R. Groh⁷  Jack Antel⁷  Jeffery A. Hall⁷  Moein Yaqubi⁷  Nicholas W. Kieran⁷  Elia Afanasiev⁷  Qiao-Ling Cui⁷  Luke M. Healy⁷  Roy Dudley⁸  Myriam Srour⁸ 

[1] Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada;Department of Electrical and Electronic Engineering, Shiraz University of Technology, Shiraz, Fars, Iran;Department of Microbiology and Immunology, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada;Department of Neurosciences, Université de Montréal, Montreal, QC, Canada;Departments of Pathology, Neurology and Neurosurgery, McGill University, Montreal, QC, Canada;Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de L, Université de Montréal (CRCHUM), Montreal, QC, Canada;Department of Neurosciences, Université de Montréal, Montreal, QC, Canada;Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada;Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada;Department of Pediatric Neurosurgery, Montreal Children’s Hospital, Montreal, QC, Canada;

关键词: scRNA-seq;    Ex vivo human microglia;    Transcriptional heterogeneity;    Gene regulatory network;   

DOI  :  10.1186/s12974-023-02809-7

 received in 2022-05-29, accepted in 2023-05-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMicroglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.MethodIn 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.ResultsWe 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.ConclusionIn 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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