Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse

Neuron 2016

Zhang, Ye and Sloan, Steven A. and Clarke, Laura E. and Caneda, Christine and Plaza, Colton A. and Blumenthal, Paul D. and Vogel, Hannes and Steinberg, Gary K. and Edwards, Michael S.B. and Li, Gordon and Duncan, John A. and Cheshier, Samuel H. and Shuer, Lawrence M. and Chang, Edward F. and Grant, Gerald A. and Gephart, Melanie G. Hayden and Barres, Ben A.

Abstract

Microglia are brain immune cells that constantly survey their environment to maintain homeostasis. Enhanced microglial reactivity and proliferation are typical hallmarks of neurodegenerative diseases. Whether specific disease-linked microglial subsets exist during the entire course of neurodegeneration, including the recovery phase, is currently unclear. Taking a single-cell RNA-sequencing approach in a susceptibility gene-free model of nerve injury, we identified a microglial subpopulation that upon acute neurodegeneration shares a conserved gene regulatory profile compared to previously reported chronic and destructive neurodegeneration transgenic mouse models. Our data also revealed rapid shifts in gene regulation that defined microglial subsets at peak and resolution of neurodegeneration. Finally, our discovery of a unique transient microglial subpopulation at the onset of recovery may provide novel targets for modulating microglia-mediated restoration of brain health.

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