Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages

Department of Gene and Cell Medicine and the Immunology Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Science (Impact Factor: 33.61). 10/2010; 330(6005):841-5. DOI: 10.1126/science.1194637
Source: PubMed


Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative
and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic
progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations,
we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor–deficient
mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise
before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte
system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain

Download full-text


Available from: E. Richard Stanley, Oct 12, 2015
61 Reads
  • Source
    • "They populate the CNS and are maintained throughout life by proliferation and by their longevity (Lawson et al., 1992; Alliot et al., 1999; Ajami et al., 2007; Ginhoux et al., 2010). In extreme experimental conditions when microglia are completely depleted from the adult CNS, they appear to be replenished by CNS resident progenitors (Elmore et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Macrophages in the injured spinal cord arise from resident microglia and from infiltrating peripheral myeloid cells. Microglia respond within minutes after central nervous system (CNS) injury and along with other CNS cells signal the influx of their peripheral counterpart. Although some of the functions they carry out are similar, they appear to be specialized to perform particular roles after CNS injury. Microglia and macrophages are very plastic cells that can change their phenotype drastically in response to in vitro and in vivo conditions. They can change from pro-inflammatory, cytotoxic cells to anti-inflammatory, pro-repair phenotypes. The microenvironment of the injured CNS importantly influences macrophage plasticity. This review discusses the phagocytosis and cytokine mediated effects on macrophage plasticity in the context of spinal cord injury. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 09/2015; DOI:10.1016/j.neuroscience.2015.08.064 · 3.36 Impact Factor
  • Source
    • "Meyer et al . , 2006 ) , a developmental age at which immature microglia , the resident immune cells of the brain , have not yet invaded the fetal central nervous system ( CNS ; Ginhoux et al . , 2010 ; Rigato et al . , 2011 ; Swinnen et al . , 2013 ) . Microglia colonize the brain early during embryonic development ( E11 . 5 in the mouse embryo ; Ginhoux et al . , 2010 ; Rigato et al . , 2011 ; Swinnen et al . , 2013 ) and are known to control several developmental processes in the brain at perinatal developmental stages ( Cunningham et al . , 2013 ; Squarzoni et al . , 2014 ; Michell - Robinson et al . , 2015 ) . First , embryonic microglia have been shown to be involved in angiogenesis through close"
    [Show abstract] [Hide abstract]
    ABSTRACT: Several studies have indicated that inflammation during pregnancy increases the risk for the development of neuropsychiatric disorders in the offspring. Morphological brain abnormalities combined with deviations in the inflammatory status of the brain can be observed in patients of both autism and schizophrenia. It was shown that acute infection can induce changes in maternal cytokine levels which in turn are suggested to affect fetal brain development and increase the risk on the development of neuropsychiatric disorders in the offspring. Animal models of maternal immune activation reproduce the etiology of neurodevelopmental disorders such as schizophrenia and autism. In this study the poly (I:C) model was used to mimic viral immune activation in pregnant mice in order to assess the activation status of fetal microglia in these developmental disorders. Because microglia are the resident immune cells of the brain they were expected to be activated due to the inflammatory stimulus. Microglial cell density and activation level in the fetal cortex and hippocampus were determined. Despite the presence of a systemic inflammation in the pregnant mice, there was no significant difference in fetal microglial cell density or immunohistochemically determined activation level between the control and inflammation group. These data indicate that activation of the fetal microglial cells is not likely to be responsible for the inflammation induced deficits in the offspring in this model.
    Frontiers in Cellular Neuroscience 08/2015; 9:301. DOI:10.3389/fncel.2015.00301 · 4.29 Impact Factor
  • Source
    • "In steady state, microglia are quiescent with very little turnover (Lawson et al., 1992), but when required, these cells can exert massive proliferation, reminiscent of their expansion when they seed the brain during embryonic development (Ginhoux et al., 2010) or during CNS inflammation (Gó mez-Nicola et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: During early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism's lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed high amounts of the interleukin-1 receptor (IL-1R), and treatment with an IL-1R antagonist during the repopulation phase impaired microglia proliferation. Hence, microglia have the potential for efficient self-renewal without the contribution of peripheral myeloid cells, and IL-1R signaling participates in this restorative proliferation process. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 07/2015; 43(1). DOI:10.1016/j.immuni.2015.06.012 · 21.56 Impact Factor
Show more