Comparative Analysis Identifies Similarities between the Human and Murine Microglial Sensomes

Erik R Abels1,2, Lisa Nieland1, Suzanne Hickman3

  • 1Departments of Neurology and Radiology, Massachusetts General Hospital, NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA.

Insights

Researchers identified a core set of 57 genes, the "microglia core sensome," conserved between mice and humans. This sensome helps understand microglial function in neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Microglia, the brain's immune cells, continuously monitor their environment using a specific gene set called the sensome.
  • The sensome comprises highly expressed surface receptors crucial for microglial environmental sensing and adaptation.

Purpose of the Study:

  • To update the mouse microglial sensome by integrating new RNA sequencing data.
  • To identify the human microglial sensome using independent human microglia RNA sequencing datasets.
  • To determine conserved and species-specific genes between mouse and human microglial sensomes.

Main Methods:

  • Integrated an additional RNA sequencing dataset to refine the mouse microglial sensome.
  • Analyzed two independent human microglia RNA sequencing datasets to identify the human sensome.
  • Compared mouse and human sensomes to identify conserved genes, defining the "microglia core sensome" (57 genes).
  • Examined the expression of core sensome genes in datasets from two neurodegenerative disease models.

Main Results:

  • Identified a conserved "microglia core sensome" of 57 genes shared between mouse and human microglia.
  • Observed species-specific differences in microglial sensome gene sets.
  • Found that changes in microglial sensome gene expression are specific to the disease or condition studied.
  • Demonstrated that microglial sensome gene expression patterns vary across different neurodegenerative disease models and stages.

Conclusions:

  • The study defines a "microglia core sensome" crucial for understanding microglial biology.
  • Results underscore the utility of mouse models for human microglia research while highlighting the need for species-specific gene sets.
  • The identified core sensome can aid in identifying pathological microglial changes in human diseases and mouse models.