GSE137444
Stem cell derived human microglia transplanted in mouse brain to study human disease
While genetics highlight the role of microglia in Alzheimer's disease (AD), one third of putative AD-risk genes lack adequate mouse orthologs. Here, we successfully engraft human microglia derived from embryonic stem cells in the mouse brain. The cells recapitulate transcriptionally human primary microglia ex vivo and show expression of human specific AD-risk genes. Oligomeric Amyloid-ß induces a divergent response in human vs. mouse microglia. This model can be used to study the role of microglia in neurological diseases. Overall design: To control for variability across different experiments, tissue from three mice was pooled in all experimental conditions, from different litters and transplanted with H9-microglia produced in independent batches of in vitro differentiation. Across the manuscript we report both the number of mice/differentiations pooled, as well as the number of sequencing pools. In summary, 1) we sequenced 2,246 transplanted H9-microglia (n=3/1, 3 mice in 1 combined sequencing pool), 4496 H9-derived monocytes (n=2/1, 2 differentiations in 1 combined sequencing pool) and 3385 microglia in vitro (n=2/1), and 22,846 human primary microglia obtained from cortical surgical resections. 2) We sequenced 4880 transplanted H9-microglia (n=3x2/2) and 9942 host mouse cells (n=3x2/2) and assessed their differential response to oligomeric amyloid beta.