Creating and Deploying a Toolkit for Human Microglia in Neurodegeneration

Recent convergent work has put a spotlight on microglial cells in the brain as a key part of the brain’s immune response in a broad range of neurodegenerative diseases. The field has lacked robust and reliable tools for dissecting the role of these cells, especially in human samples. To address this gap, this team will generate key reference data and a microglia experimental toolkit to identify and target different human microglial subtypes, with plans to make these tools available to the broader research community.

The team developed a new catalog of single-cell RNA-seq signatures of live human microglia (brain resident immune cells) isolated from 180 individuals with neurological diseases including Alzheimer’s, Parkinson’s, ALS, and MS. These signatures were grouped into a taxonomy of 12 putative microglial states, some of which showed enrichment of disease-associated genes. The presence of these signatures was confirmed in brain tissue sections, followed by the identification and validation of small molecule compounds predicted to shift polarized microglial-like cells in vitro.