Neuro-immune organoid model reveals a role of microglia in cell stress response and emergence of neural activity

Purpose: Many 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. Methods: By using 10X Genomics scRNAseq, we generated transcriptomic data across different microglia models. Additionally, we performed microglia engraftment into cortical brain organoids and analyzed molecular changes in different cell types occurring in response to the presence of microglia. Results: We compared human microglia states across culture models, including cultured primary microglia and pluripotent stem cell-derived microglia and developed a 'report card' of gene expression signatures differentially recruited and attenuated across these distinct experimental models. Overall design: Single-cell RNA sequencing profliling of microglia transcriptional states in response to different in vitro model conditions