Böttcher C, Schlickeiser S, Sneeboer MA, Kunkel D, Knop A, Paza E, Fidzinski P, Kraus L, Snijders GJ, Kahn RS, Schulz AR, Mei HE, NBB-Psy, Hol EM, Siegmund B, Glauben R, Spruth EJ, de Witte LD, Priller J. Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. Nat Neurosci. 2019 Jan;22(1):78-90. Epub 2018 Dec 17 PubMed.

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  1. This paper provides an important technical advance, as it defines a reliable and standardized procedure for the analysis of human microglia from postmortem brain tissues, providing high resolution and preventing batch effects.

    Conceptually, the paper defines phenotypic criteria to distinguish microglia from other brain macrophages, such as perivascular macrophages, and identifies IRF8 expression as a marker to distinguish postmortem vs. fresh samples. Importantly, the study defines cell surface molecules that enable us to dissect some regional heterogeneity of microglia in human brain. Once again, this result underscores the impact of microenvironment in the diversification of tissue resident cells.

    The major question this paper raises is what is the functional impact of this diversity beyond the phenotypic characterization? Do microglia have different functional properties in different brain regions? Do they specialize in specific functions? Another important question is which microenvironmental factors drive this diversity? These are crucial questions for future studies.

    View all comments by Marco Colonna

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