Macrophage heterogeneity in the single cell era: facts and artefacts.

In this spotlight we review technical issues that compromise single cell analysis of tissue macrophages including limited and unrepresentative yields, fragmentation and generation of remnants and activation during tissue disaggregation. These issues may lead to misleading definition of subpopulations of macrophages and expression of macrophage-specific transcripts by unrelated cells. Recognition of the technical limitations of single cell approaches is required in order to map the full spectrum of tissue resident macrophage heterogeneity and to assess its biological significance.