Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies.

Anouk Benmamar-Badel,Agnieszka Wlodarczyk,Trevor Owens

doi:10.3389/fimmu.2020.00430

Anouk Benmamar-Badel, Agnieszka Wlodarczyk + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2020.00430

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Abstract

Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these “microglial signatures” have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced.

Highlights

The term “microglia” was brought to the scientific community’s attention a century ago with its first use by Pio del Rio-Hortega [1], who strived to distinguish them from oligodendrocytes
Expression of Igf1 and colonystimulating factor 1 (Csf1) by microglia were hypothesized to play a protective role, preventing axonal damage for instance, which has since been confirmed in a study by Ueno et al [12]. This finding was reinforced by our own study showing that microglial cells expressing high levels of Itgax and Igf1 are present in the white matter of developing mouse brains between P3 and P5 where they make up almost 20% of all microglia and decrease in numbers already at P7 before being almost completely undetectable by P28 [35]
Comparison of the developmental signature and the disease signature resulted in defining of a “core” signature common to CD11c+ microglia across all contexts, which consists of 22 genes: Ank, Anxa5, Aplp2, Atp1a3, Clec7a, Colec12, Csf1, Ephx1, Fabp5, Fam20c, Gm1673, Gpnmb, Hpse, Igf1, Itgax, Lilrb4, Lpl, Nceh1, Plaur, Pld3, Plin2, and Spp1 (Figure 3 and Supplementary Table 1)

Summary

Introduction

The term “microglia” was brought to the scientific community’s attention a century ago with its first use by Pio del Rio-Hortega [1], who strived to distinguish them from oligodendrocytes. This finding was reinforced by our own study showing that microglial cells expressing high levels of Itgax and Igf1 are present in the white matter (cerebellum and corpus callosum) of developing mouse brains between P3 and P5 where they make up almost 20% of all microglia and decrease in numbers already at P7 before being almost completely undetectable by P28 [35].

Results

Conclusion