Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer's disease [scRNA-seq]

Amyloid plaque associated microglia induce a transcriptional state characterized by downregulation of the transcription factor Spi1 and upregulation of a subset of canonically lymphoid-specific signaling genes. Knockout of one such gene, Cd28, in microglia exacerbates interferon-responses in response to amyloid pathology. Overall design: Wild type, 5xFAD, and 5xFAD; Cd28-cKO (microglia specific KO generated by breeding 5xFAD, Cd28fl/fl mice to Cx3cr1creERT2/+ mice and gavaged 6x with tamoxifen) were aged to 3, 6, or 8 months of age. Microglia were isolated by removing forebrain, homogenizing tissue, preparing single cell suspensions using Percoll, and sorting microglia using fluorescent antibodies against CD45 and CD11b (collecting CD45-intermediate, CD11B+ cells as microglia). 10,000 cells per sample were submitted for 10X Single Cell RNA-sequencing.