Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation

Abstract

The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain’s innate immune system.

Comparative analysis of CreER transgenic mice for the study of brain macrophages: A case study

“…As reported earlier, Cx 3 cr1 CreER transgenic animals display rearrangements in BAM , and BAM signature genes such as Lyve1 and Pf4 were hence found enriched in HA IP samples of their brain (Fig. 1F).…”

“…3C–E, ). As previously reported , Cx 3 cr1 CreER : R26/CAG‐tdTomato mice showed exclusive reporter gene expression in CD11b + CD45 + cells, comprising microglia and BAM. In contrast, Sall1 CreER :R26/CAG‐tdTomato mice displayed a prominent population of labeled CNS cells negative for the pan hematopoietic marker CD45 that likely represent astrocytes and oligodendrocytes (Fig.…”

Gene expression profiling reveals a conserved microglia signature in larval zebrafish

“…Recent single-cell RNA sequencing studies of rodent and human microglia revealed specific time-and region-dependent subtypes of microglia (Hammond et al, 2019;Jordão et al, 2019;Li et al, 2019;Masuda et al, 2019). Future studies will have to reveal if similar subtypes also exist during zebrafish development.…”

Microglia/macrophage diversities in central nervous system physiology and pathology

“…A cluster of Apoe + Ccl5 + microglia has been observed at the onset of recovery from nerve injury . A recent study showed that CNS‐resident macrophages also quickly transformed into context‐dependent subsets during brain inflammation . In addition, bone marrow‐derived macrophages that infiltrate into the brain in case of blood‐brain barrier breach bring in more subsets of myeloid cells .…”