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Microglia modulate neurodevelopment in human neuroimmune organoids

Authors :
Mariko L. Bennett
Hongjun Song
Guo-li Ming
Source :
Cell Stem Cell
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Microglia are resident macrophages in the brain that emerge in early development and respond to local environment by altering their molecular and phenotypic states. Fundamental questions about microglia diversity and function during development remain unanswered as we lack experimental strategies to interrogate their interactions with other cell types and responses to perturbations ex vivo. We compared human microglia states across culture models, including cultured primary and pluripotent stem cell-derived microglia. We developed a ‘report card’ of gene expression signatures across these distinct models to facilitate characterization of their responses across experimental models, perturbations, and disease conditions. Xenotransplantation of human microglia into cerebral organoids allowed us to characterize key transcriptional programs of developing microglia in vitro and reveal that microglia induce transcriptional changes in neural stem cells and decreases interferon signaling response genes. Microglia additionally accelerate the emergence of synchronized oscillatory network activity in brain organoids by modulating synaptic density.

Details

ISSN :
19345909
Volume :
28
Database :
OpenAIRE
Journal :
Cell Stem Cell
Accession number :
edsair.doi.dedup.....cfd48bdaea8620340bbdd03ba8240638
Full Text :
https://doi.org/10.1016/j.stem.2021.11.005