Unique microglia recovery population revealed by single-cell RNAseq following neurodegeneration

Acta Neuropathol Commun. 2018 Sep 5;6(1):87. doi: 10.1186/s40478-018-0584-3.

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.

Keywords: Microglia; Neurodegeneration; Recovery; Single-cell RNA analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axotomy / methods
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • Calcium-Binding Proteins / metabolism
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Facial Nerve Injuries / complications
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Microglia / metabolism*
  • Microglia / pathology
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / pathology*
  • Neurodegenerative Diseases / physiopathology*
  • Recovery of Function / physiology*
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis

Substances

  • Aif1 protein, mouse
  • CX3C Chemokine Receptor 1
  • Calcium-Binding Proteins
  • Cx3cr1 protein, mouse
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Green Fluorescent Proteins