Kia M Barclay

10.1016/j.immuni.2024.05.005 Author MSS Microglia, Animals, Mice, Remyelination, Cell Plasticity, Demyelinating Diseases, Mice, Inbred C57BL, Mice, Transgenic, Disease Models, Animal, Brain, Myelin Sheath, White Matter, Microglia, Alzheimer’s Disease, Multiple Sclerosis, Development, Single-cell RNA Sequencing, Proliferative-Region Associated Microglia, Disease-Associated Microglia, Heterogeneity, Clec7a-CreER, Plasticity, Depletion yes Barclay, Kia M; Abduljawad, Nora; Cheng, Zuolin; et al.,...

Tamoxifen delivery For Runx1-CreERT2 and Cdh5-CreERT2 lineage tracing experiments, a mixture of 1.5mg (Z)-4-Hydroxytamoxifen (Sigma H7904-25MG) and 0.75mg progesterone (to counteract estrogen agonist effects of tamoxifen) prepared in 500uL corn oil was intraperitoneally administered to a pregnant mouse carrying E7.0 or E6.5 embryos respectively. For PAM labeling, a single 10uL dose of 10mg/mL tamoxifen solution prepared in corn oil was subcutaneously injected into each P4 pup.

Highlights • Generation of a Clec7a-CreERT2 mouse model to study specific microglial states • scRNA-seq of labeled PAMs and DAMs reveals convergent and divergent gene signatures • Tracking microglial states in vivo reveals context-dependent plasticity • State-specific ablation shows DAMs are protective and required for remyelination Summary Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease.