Origin, fate and dynamics of macrophages at CNS interfaces

By Tobias Goldmann, P. Wieghofer, M. J. C. Jordão, Fabiola Prutek, N. Hagemeyer, Kathrin Frenzel, Lukas Amann, O. Staszewski, Katrin Kierdorf, M. Krueger and 12 more. Nature Immunology, 2016

1,006 citations recorded by the source corpus.

Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required.

Subfields: Developmental Neuroscience, Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/8986989fd1c3a7c75c50467cac6e0e9946c92006

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Citations in the corpus

High‐Dimensional Single‐Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease (2018, positive): “Combining Lyve1 or MHCII with the macrophage marker Iba-1, we located BAMs within the pia mater, perivascular space, choroid plexus, and dura mater and showed that they express CD206, as previously shown (Figure S4B; Goldmann et al., 2016).”
Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes (2018, background): “A Population of Embryonic Ms4a-Expressing Microglia Share a Similar Transcriptional Profile with Brain Border Macrophages Microglia and brain border macrophages (which reside in the perivascular space, meninges, and choroid plexus) are derived from the same pool of yolk sac hematopoietic progenitors”
Microglia states and nomenclature: A field at its crossroads (2022, critical): “Thus, although still widely used, ‘‘resting’’ and ‘‘activated’’ microglia are labels that should be discontinued. represent their transcriptional identity and are commonly employed as ‘‘microglial markers’’ (Table 1).”
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation (2019, background): “hCAM3 also showed high levels of Ccr2 due to the contribution of cpMF, which are known to be partially derived from CCR2 monocytes (24).”
The microenvironmental landscape of brain tumors (2017, background): “Similarly, non-parenchymal macrophages within the CNS arise during embryonic development, and are largely stable populations during adult life (Goldmann et al., 2016).”
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “73 The in ﬁ ltration of monocyte-derived macrophages (MDMs), which have a higher phagocytic activity than microglia, promotes tissue repair and the resolution of in ﬂ ammation.”
Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017, background): “However, a recent study showed that perivascular and meningeal macrophages are, in fact, long-lived macrophages that derive from primitive progenitors (3).”