Macrophage heterogeneity in the single-cell era: facts and artifacts

David A Hume1, Susan M Millard1, Allison R Pettit1

  • 1Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.

Blood
|August 18, 2023
PubMed

Insights

Technical challenges in single-cell analysis can distort findings on tissue macrophages. Addressing these limitations is crucial for accurately understanding macrophage heterogeneity and function.

Area of Science:

  • Immunology
  • Cell Biology
  • Genomics

Background:

  • Single-cell analysis offers high resolution for studying cell heterogeneity.
  • Tissue macrophages play critical roles in immunity and tissue homeostasis.
  • Understanding macrophage heterogeneity is essential for disease research.

Approach:

  • Review of technical limitations in single-cell analysis of tissue macrophages.
  • Identification of issues including cell yield, sample integrity, and dissociation artifacts.
  • Analysis of how these technical factors impact data interpretation.

Key Points:

  • Limited and unrepresentative cell yields compromise macrophage population analysis.
  • Sample fragmentation and remnant generation create analytical noise.
  • Cell activation during tissue disaggregation alters macrophage gene expression profiles.
  • These technical issues can lead to misidentification of macrophage subpopulations.
  • Artifactual expression of macrophage transcripts in non-macrophage cells is a concern.

Conclusions:

  • Awareness of technical limitations is paramount for accurate single-cell macrophage studies.
  • Overcoming these challenges is necessary to fully map tissue-resident macrophage heterogeneity.
  • Accurate assessment of macrophage heterogeneity is vital for understanding its biological significance in health and disease.

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