Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry

Chotima Böttcher1, Stephan Schlickeiser2, Marjolein A M Sneeboer3

  • 1Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. chotima.boettcher@charite.de.

Nature Neuroscience
|December 19, 2018
PubMed

Insights

Human microglia (huMG) heterogeneity was characterized using mass cytometry. This study reveals distinct huMG phenotypes across brain regions, crucial for understanding neurological health and disease.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key innate immune cells in the central nervous system (CNS), vital for neural development and function.
  • Limited understanding of human microglia (huMG) heterogeneity due to procurement and preservation challenges.
  • Rodent microglia phenotypes are known, but human counterparts remain understudied.

Purpose of the Study:

  • To comprehensively characterize human microglia heterogeneity using advanced techniques.
  • To define the phenotypic signature of human microglia and compare it to peripheral myeloid cells.
  • To investigate regional variations in microglia phenotypes within the human brain.

Main Methods:

  • Application of multiplexed mass cytometry for high-dimensional immunophenotyping.
  • Analysis of 57 markers on a large scale (10^3 - 10^4 cells) from postmortem human brain samples.
  • Utilized a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis.

Main Results:

  • Identified a distinct phenotypic signature for human microglia, differing from peripheral myeloid cells.
  • Demonstrated that postmortem huMG phenotypes are comparable to fresh human microglia.
  • Detected significant regional heterogeneity in microglia phenotypes across different brain areas.

Conclusions:

  • Established a robust methodology for large-scale, single-cell level immunophenotyping of human microglia.
  • Provided critical insights into human microglia heterogeneity and regional specialization.
  • Facilitated unambiguous profiling of human microglia in both healthy and diseased states.

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