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

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    • "The NG2 glia, lineage-related to oligodendrocytes, may be involved in myelination/remyelination in the adult brain as well as contribute to general housekeeping (Nishiyama and others 2009; Richardson and others 2011). Microglial cells originate from c-kit+ erythromyeloid precursors present in the extra-embryonic yolk sac (Kierdorf and others 2013), which invade neural tube very early (at E10 in mice (Ginhoux and others 2010)) in embryogenesis. Microglial precursors disseminate throughout the CNS and undergo transformation into ramified microglia, characterised by specific morphology (small cell body and long, thin motile processes) and physiology (expression of extended complement of receptors to neurotransmitters and neurohormones, as well as classic " immune " receptors, such as Toll-like receptors, and receptors to chemokines/cytokines; "
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    • "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). "
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    • "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"
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    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.
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