The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
The origin and cell lineage of microglia: new concepts
Abstract
Despite intense study, the precise origin and cell lineage of microglia, the resident mononuclear phagocytes of the nervous system, are still a matter for debate. Unlike macroglia (astrocytes and oligodendrocytes) and neurons, which are derived from neuroectoderm, microglial progenitors arise from peripheral mesodermal (myeloid) tissue. The view still commonly held is that tissue-resident mononuclear phagocytes (including microglia) are derived from circulating blood monocytes and these take up residence late in gestation and postnatally. However, microglial progenitors colonise the nervous system primarily during embryonic and fetal periods of development. Recent evidence indicates differences between the lineage of mononuclear phagocytes during the embryonic and fetal period from that in the neonate and adult-mononuclear phagocytes that take up residence within tissues are derived from a lineage of myeloid cells that is independent of the monocyte lineage. Our own findings on the development and differentiation of microglial progenitors, taken together with findings by other investigators, and in the context of the heterogeneity between myeloid differentiation in the fetus and in the adult, support the view that microglia are derived prenatally from mesodermal progenitors that are distinct from monocytes. Furthermore, microglial progenitors colonise the nervous system via extravascular routes initially. These findings challenge the concept that resident microglia in the nervous system are derived from circulating blood monocytes. Work is still underway to establish the tissue of origin and lineage of microglial progenitors in vivo. This information is critical not only from a developmental perspective, but significantly from a therapeutic viewpoint, as (i) the unique property of microglial progenitors to colonise the nervous system from the periphery allows these cells to be exploited as a biological and non-invasive means for cell therapy by delivering genes to the nervous system (microglial engraftment), and (ii) there are indications that microglial progenitors are specifically able to home to the nervous system. Use of microglial progenitors for therapeutic purposes becomes feasible only if the origin and cell lineage of these microglial progenitors are known and these cells can be isolated and manipulated in vitro (i.e., to express specific trophic factors) prior to therapeutic transfer (e.g., intravenously) in vivo. In this paper, we shall briefly consider the existing concepts on the origin and lineage of microglial progenitors and discuss new hypotheses in the light of emerging data that suggest clear differences between fetal and adult ontogeny of myeloid cells.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Subsequent reports showed that microglia arise early during development from progenitors in the embryonic yolk sac4,38,39.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [39]
In the citing paper
“Iba1+/Dab2+ cells resembled the early fetal macrophages previously reported in the developing CNS [35], several of which were found in the proximity of blood vessels at E10.5 (Fig 3D) and E11.5 (Fig 3E).”
From Dynamic expression of Dab2 in the mouse embryonic central nervous system (2008) · cites this paper as [35]
In the citing paper
“these results allude to differences in myeloid cell differentiation (and/or commitment) between macrophages and microglial cells [35]”
From Dynamic expression of Dab2 in the mouse embryonic central nervous system (2008) · cites this paper as [35]
In the citing paper
“PU.1 is an essential factor required for myeloid cell differentiation [35].”
From Dynamic expression of Dab2 in the mouse embryonic central nervous system (2008) · cites this paper as [35]
In the citing paper
“These observations may imply that at least a subpopulation of early microglia (Iba1+/Dab2+) are derived from myeloid progenitors migrating into neural tube via microvessels, rather than derived in situ [35].”
From Dynamic expression of Dab2 in the mouse embryonic central nervous system (2008) · cites this paper as [35]
In the citing paper
“Many of these cytokines are known to be highly elevated in neurological diseases and/or involved in the recruitment of peripheral immune cells into the CNS under pathological conditions”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Chan et al., 2007
Citations
Cites
Perry, V. H., Hume, D. A., & Gordon, S. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90215-5 · Cited by 902
Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain
Alliot, F., Godin, I., & Pessac, B. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00113-3 · Cited by 884
Priller, J., Flügel, A., Wehner, T., Boentert, M., Haas, C. A., Prinz, M., Fernández-Klett, F., Prass, K., Bechmann, I., de Boer, B. A., et al. (2001) · Nature Medicine · doi:10.1038/nm1201-1356 · Cited by 637
Simard, A. R., & Rivest, S. (2004) · The FASEB Journal · doi:10.1096/fj.04-1517fje · Cited by 362
Kennedy, D. W., & Abkowitz, J. L. (1997) · Blood · doi:10.1182/blood.v90.3.986 · Cited by 342
MafB is an inducer of monocytic differentiation
Kelly, L. M., Englmeier, U., Lafon, I., Sieweke, M. H., & Graf, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.9.1987 · Cited by 308
The origin and differentiation of microglial cells during development
Cuadros, M. Á. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00035-5 · Cited by 305
Hematopoietic origin of microglial and perivascular cells in brain
Hess, D. C., Abe, T., Hill, W., Martin-Studdard, A., Carothers, J., Masuya, M., Fleming, P. A., Drake, C. J., & Ogawa, M. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.11.005 · Cited by 281
Biffi, A., Palma, M. D., Quattrini, A., Carro, U. D., Amadio, S., Visigalli, I., Sessa, M., Fasano, S., Brambilla, R., Marchesini, S., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419205 · Cited by 280
Biffi, A., Palma, M. D., Quattrini, A., Carro, U. D., Amadio, S., Visigalli, I., Sessa, M., Fasano, S., Brambilla, R., Marchesini, S., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19205 · Cited by 261
Flagged first, then by citations
Research works printed but not linked: 1
- Jeetle, 2002, Microglia in the CD11b knockout mouse, Neuroembryology, 1, 191
Cited by
Sorted by citations
Items 101–200 of 401
Augusto‐Oliveira, M., Arrifano, G. D. P., Delage, C. I., Tremblay, M., Lopez, M. E. C., & Verkhratsky, A. (2021) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12797 · Cited by 114
“Microglial progenitors stained with anti-IBA1 antibodies can be detected within the developing nervous system as early as E11 in mice (Chan et al., 2007), and IBA1 is subsequently expressed by microglia throughout life in both surveilling and reactive phenotypes across the CNS.”
BackgroundUnique transcriptome signature of mouse microglia
Beutner, C., Linnartz‐Gerlach, B., Schmidt, S. V., Beyer, M., Mallmann, M. R., Staratschek‐Jox, A., Schultze, J. L., & Neumann, H. (2013) · Glia · doi:10.1002/glia.22524 · Cited by 112
“, 2012) and then locally proliferate within the CNS to increase their number until around birth to finally become adult microglia (Alliot et al., 1999; Chan et al., 2007).”
BackgroundNeuron-Interacting Satellite Glial Cells in Human Trigeminal Ganglia Have an APC Phenotype
van Velzen, M., Laman, J. D., KleinJan, A., Poot, A. M., Osterhaus, A. D. M. E., & Verjans, G. M. G. M. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900890 · Cited by 106
“Whereas macroglia, like astrocytes and oligodendrocytes, are derived from the neuroectoderm (31), microglia express several leukocyte cell markers implicating their origin from myeloid progenitor cells (26, 32).”
BackgroundTerasaki, L. S., & Schwarz, J. M. (2016) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-016-9691-8 · Cited by 110
“To that end, we administered alcohol to pregnant dams from E10-E16, a time during which microglia first colonize the fetal rat brain (Chan et al. 2007; Cuadros and Navascues 1998).”
BackgroundMethodProteomic analysis of aged microglia: shifts in transcription, bioenergetics, and nutrient response
Flowers, A., Bell‐Temin, H., Jalloh, A., Stevens, S. M., & Bickford, P. C. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0840-7 · Cited by 107
“synaptic function through pruning, a necessary process for learning consolidation [9].”
BackgroundRegulation of brain microglia by female gonadal steroids
Habib, P., & Beyer, C. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.02.018 · Cited by 118
Rigato, C., Buckinx, R., Corronc, H. L., Rigo, J., & Legendre, P. (2011) · Glia · doi:10.1002/glia.21140 · Cited by 102
“mouse embryo, it occurs as early as embryonic age 9–11 days (E9–E11), both in the brain and in the retina (Chan et al., 2007; Santos et al., 2008).”
BackgroundArnoux, I., Hoshiko, M., Mandavy, L., Avignone, E., Yamamoto, N., & Audinat, É. (2013) · Glia · doi:10.1002/glia.22503 · Cited by 96
“…cells and neurons, which are of neuroec-toderm origin, microglial cells derive from myeloid progenitors born in the yolk sac that enter the brain during early embryonic life (Alliot et al., 1999; Chan et al., 2007; Cuadros et al., 2001; Ginhoux et al., 2010; Ling et al., 2001; Schulz et al., 2012).”
BackgroundMorgan, J. T., Barger, N., Amaral, D. G., & Schumann, C. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110356 · Cited by 97
Latta, C. H., Sudduth, T. L., Weekman, E. M., Brothers, H. M., Abner, E. L., Popa, G. J., Mendenhall, M. D., Gonzalez-Oregon, F., Braun, K. J., & Wilcock, D. M. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0243-6 · Cited by 96
“Background: Microglia are considered the resident immune cells of the central nervous system (CNS).”
BackgroundInfluentialLong Lasting Local and Systemic Inflammation after Cerebral Hypoxic ischemia in Newborn Mice
Winerdal, M., Winerdal, M. E., Kinn, J. M., Urmaliya, V., Winqvist, O., & Ådén, U. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036422 · Cited by 92
“Microglial cells have a common progenitor with monocytes and share CD11b and CD11c markers [27].”
BackgroundOhsawa, K., & Kohsaka, S. (2011) · Glia · doi:10.1002/glia.21238 · Cited by 92
“…sources: one population is generated from bone marrow-derived cells that migrate to the CNS during embryonic development, and the second is derived from myeloid progenitor cells that enter the brain after birth (Chan et al., 2007; Ginhouxet al., 2010; Mildner et al., 2007; Prinz and Mildner, 2011).”
BackgroundEmerging Concepts in Myeloid Cell Biology after Spinal Cord Injury
Hawthorne, A. L., & Popovich, P. G. (2011) · Neurotherapeutics · doi:10.1007/s13311-011-0032-6 · Cited by 94
Role of microglia-neuron interactions in diabetic encephalopathy
Liu, Y., Li, M., Zhang, Z., Ye, Y., & Zhou, J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.12.005 · Cited by 88
The origins and non-canonical functions of macrophages in development and regeneration
Théret, M., Mounier, R., & Rossi, F. M. V. (2019) · Development · doi:10.1242/dev.156000 · Cited by 90
“5-E9 (Alliot et al., 1999; Herbomel et al., 2001; Ajami et al., 2007; Chan et al., 2007; Ginhoux et al., 2010; Hashimoto et al., 2013; Salter and Beggs, 2014), before the origins of the first HSCs and of most adult MPs.”
BackgroundBrain-Region-Specific Astroglial Responses In Vitro After LPS Exposure
Kipp, M., Norkutė, A., Johann, S., Lorenz, L., Braun, A., Hieble, A., Gingele, S., Pott, F., Richter, J., & Beyer, C. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-008-9057-7 · Cited by 86
“Since microglial progenitors arise from peripheral mesodermalmyeloid tissue (Chan et al. 2007), CSFs secreted from astrocytes are likely candidates for astroglial–microglia interactions.”
BackgroundGeneration of microglial cells from mouse embryonic stem cells
Beutner, C., Roy, K., Linnartz, B., Napoli, I., & Neumann, H. (2010) · Nature Protocols · doi:10.1038/nprot.2010.90 · Cited by 85
“They appear as ionized calcium-binding adaptor molecule-1 (Iba1)-positive cells within the neuroepithelium during early neuroectodermal development, before vasculature has develope”
BackgroundMicroglia-mediated neuroinflammation is an amplifier of virus-induced neuropathology
Sarma, J. D. (2013) · Journal of NeuroVirology · doi:10.1007/s13365-013-0188-4 · Cited by 87
“In contrast to neurons and macroglia (i.e., astrocytes and oligodendrocytes), microglial cells are thought to derive from myeloid precursors (Chan et al. 2007).”
BackgroundInfluentialPrenatal stress alters microglial development and distribution in postnatal rat brain
Gómez‐González, B., & Escobar, A. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0590-4 · Cited by 86
“Several hypotheses have been proposed in relation to the origin of microglia; microglia have been considered to be of mesodermal, neuroectodermal (similar to astrocytes and oligodendrocytes) or monocytic origin [10, 28].”
BackgroundMicroglia activation is associated with IFN-α induced depressive-like behavior
Wachholz, S., Eßlinger, M., Plümper, J., Manitz, M. P., Juckel, G., & Friebe, A. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.09.016 · Cited by 84
In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence
Hillmer, A. T., Sandiego, C. M., Hannestad, J. O., Angarita, G. A., Kumar, A., McGovern, E. M., Huang, Y. H., O’Connor, K. C., Carson, R. E., O’Malley, S. S., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.10 · Cited by 86
“This microglial activation is a key process in the initiation and maintenance of neuroinflammation 7-9 .”
Strategies for retinal repair: cell replacement and regeneration
Lamba, D. A., Karl, M., & Reh, T. A. (2009) · Progress in brain research · doi:10.1016/s0079-6123(09)17502-7 · Cited by 81
“Microglial cells, of mesodermal origin (Chan et al., 2007) are also present in the retina.”
BackgroundBadoer, E. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.07.005 · Cited by 80
Marín‐Padilla, M., & Knopman, D. S. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31823ac627 · Cited by 78
“It is now believed that microglia migrate into the cerebral cortex during embryological development and do not enter the CNS during adulthood (43).”
Noumbissi, M. E., Galasso, B., & Stins, M. F. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0097-2 · Cited by 79
Redox Signaling, Neuroinflammation, and Neurodegeneration
Aguilera, G., Colín-González, A. L., Rangel‐López, E., Chavarría, A., & Santamaría, A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7099 · Cited by 81
“Microglia, unlike macrophages, present self-renewal and longevity characteristics (27, 53, 188).”
Linnartz‐Gerlach, B., Kopatz, J., & Neumann, H. (2014) · Glycobiology · doi:10.1093/glycob/cwu044 · Cited by 77
“Later in embryonic development, the ionized calcium-binding adaptor molecule-1 (Iba1/Aif1)positive microglial precursors proliferate locally within the CNS to become adult microglia (Chan et al. 2007).”
BackgroundGuglielmetti, C., Le Blon, D., Santermans, E., Salas-Perdomo, A., Daans, J., De Vocht, N., Shah, D., Hoornaert, C., Praet, J., Peerlings, J., et al. (2016) · Glia · doi:10.1002/glia.23053 · Cited by 76
“Microglia, wellrecognized as brain tissue-specific macrophages (Chan et al., 2007; Ginhoux et al., 2010, 2013; Tambuyzer et al., 2009), have the unique capacity to sense alterations of the brain microenvironment, and in response rapidly migrate, proliferate, and undergo specific differentiation programs to restore bra…”
BackgroundNeonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus
Boschen, K. E., Ruggiero, M., & Klintsova, A. Y. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.03.033 · Cited by 72
“The rodent immune systembegins development during gestation and continues through the first two weeks of neonatal life, with microglia beginning colonization on embryonic days 9–10 in a brain-region-specific manner (Chan et al., 2007;Ginhoux et al., 2010).”
BackgroundMicroglia Ontology and Signaling
ElAli, A., & Rivest, S. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00072 · Cited by 75
“4:72. doi: 10.3389/fcell.2016.00072 Microglia Ontology and Signaling Ayman ElAli 1 and Serge Rivest 2* 1Neuroscience Laboratory, CHU de Québec Research Center (CHUL), Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, CA, Canada, 2Neuroscience Laboratory, CHU…”
BackgroundInfluentialSherer, M. L., Posillico, C. K., & Schwarz, J. M. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.06.016 · Cited by 76
Nitric oxide-mediated tumoricidal activity of murine microglial cells
Brantley, E. C., Guo, L., Zhang, C., Lin, Q., Yokoi, K., Langley, R. R., Kruzel, E., Maya, M., Kim, S. W., Kim, S.-J., et al. (2010) · Translational Oncology · doi:10.1593/tlo.10208 · Cited by 71
“Importantly, these data also corroborate previous reports that unlike other glial cells, such as astrocytes and oligodendrocytes that originate in the neuroectoderm, microglia are derived from circulating blood monocytes and are capable of repopulating the brain during pathologic conditions [25,26,30, 44,56–59].”
ResultCold pre‐conditioning neuroprotection depends on TNF‐α and is enhanced by blockade of interleukin‐11
Mitchell, H. M., White, D. M., Domowicz, M. S., & Kraig, R. P. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07103.x · Cited by 68
SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia
Lloyd-Burton, S. M., York, E. M., Anwar, M. A., Vincent, A. J., & Roskams, A. J. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3585-12.2013 · Cited by 67
“They are derived from progenitors in the yolk sac, and enter the CNS during early embryonic development (Chan et al., 2007).”
BackgroundChiurchiù, V., Leuti, A., & Maccarrone, M. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9584-2 · Cited by 68
“Astrocytes These cells are the most abundant in the whole CNS, and like neurons and oligodendrocytes they derive from the neuroectoderm (Chan et al. 2007).”
BackgroundWang, J.-W., Chen, S.-D., Zhang, X.-L., & Jonas, J. B. (2016) · Journal of Glaucoma · doi:10.1097/ijg.0000000000000200 · Cited by 69
Ritz, B. W., Alexander, G. M., Nogusa, S., Perreault, M. J., Peterlin, B. L., Grothusen, J. R., & Schwartzman, R. J. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2010.04308.x · Cited by 71
Andrews, J. A., & Neises, K. D. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07545.x · Cited by 68
The role of the M1/M2 microglia in the process from cancer pain to morphine tolerance
Tu, H., Chu, H., Guan, S., Hao, F., Xu, N., Zhao, Z., & Liang, Y. (2020) · Tissue and Cell · doi:10.1016/j.tice.2020.101438 · Cited by 66
Ohja, K., Gozal, E., Fahnestock, M. L., Cai, L., Cai, J., Freedman, J. H., Switala, A., El-Baz, A. S., & Barnes, G. N. (2018) · NeuroMolecular Medicine · doi:10.1007/s12017-018-8488-8 · Cited by 66
“They are activated when exposed to triggers and can then carry out diverse functions which could prove to be either effective or harmful (Chan et al. 2007; Ransohoff and Perry 2009).”
BackgroundPesticides, Microglial NOX2, and Parkinson's Disease
Taetzsch, T., & Block, M. L. (2013) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.21464 · Cited by 62
“In addition to their role in innate immunity and host defense [26, 32], microglia also serve many regulatory functions in the adult CNS, where they guide neural stem cells to sites of injury [33], influence stem cell differentiation [33], regulate synaptic plasticity [34], and provide neurotrophic support [35].”
BackgroundInfluentialOxidative Stress and Neurobiology of Demyelination
Ljubisavljević, S. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-9041-x · Cited by 60
“These two processes are regulated independently so that circulating cells can migrate only into the perivascular space without the possibility of passing into CNS parenchyma, if the glial membrane is morphologically and functionally intact [6].”
BackgroundMicroglial response to aging and neuroinflammation in the development of neurodegenerative diseases
Han, T., Xu, Y., Sun, L., Hashimoto, M., & Wei, J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385845 · Cited by 64
“Despite some controversies about whether microglia originate from the mesoderm or the ectoderm (Chan et al., 2007; Ginhoux et al., 2013), some researchers still followed Pío del Rıó Hortega’s hypothesis and confirmed it by light microscopy analysis and immunohistochemistry (Hortega, 1918; Del…”
BackgroundRosenberg, J. B., Sondhi, D., Rubin, D. G., Monette, S., Chen, A., Cram, S., De, B. P., Kaminsky, S. M., Sevin, C., Aubourg, P., et al. (2014) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2013.239 · Cited by 58
“Given the slow pace of brain microglia replacement by bone marrow-derived cells, hematopoietic stem cell gene therapy may not be able to prevent the rapid cerebral demyelination that occurs in early and late infantile forms of MLD (Krivit et al., 1995; Kennedy and Abkowitz, 1997; Chan et al., 2007).”
BackgroundCalderó, J., Brunet, N., Ciutat, D., Hereu, M., & Esquerda, J. E. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22084 · Cited by 58
“Current reports indicate that they are derived from precursors related to the mesenchyme or monocyte/macrophage cell lineage, which invade the CNS during development (Cuadros and Navascués, 1998; see also Chan et al., 2007).”
BackgroundTakahashi, Y., Yu, Z., Sakai, M., & Tomita, H. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00144 · Cited by 58
“Furthermore, both microglia and monocytes are activated by and release pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8 or TNF-α (Chan et al., 2007; Schmitz et al., 2009; Beumer et al., 2012).”
BackgroundMonocytes and Alzheimer’s disease
Feng, Y., Li, L., & Sun, X. (2011) · Neuroscience Bulletin · doi:10.1007/s12264-011-1205-3 · Cited by 53
Dolga, A. M., Letsche, T., Gold, M., Doti, N., Bacher, M., Chiamvimonvat, N., Dodel, R. C., & Culmsee, C. (2012) · Glia · doi:10.1002/glia.22419 · Cited by 52
“Microglial cells are the immune competent cells in the central nervous system originating from the peripheral mesodermal tissue during early postnatal development (Chan et al., 2007).”
BackgroundUeno, M., & Yamashita, T. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.02.004 · Cited by 56
Role of Microglia in Modulating Adult Neurogenesis in Health and Neurodegeneration
Al‐Onaizi, M., Al-Khalifah, A., Qasem, D., & ElAli, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186875 · Cited by 60
“Some findings suggest that microglia originate from progenitors derived from the neuroectoderm and/or the mesoderm to invade the brain [1], while other new findings suggest that an additional pool of microglia may derive from circulating progenitors, namely the monocytes [3].”
BackgroundDevelopment and characterization of a human microglia cell model of HIV-1 infection
Rawat, P., & Spector, S. A. (2016) · Journal of NeuroVirology · doi:10.1007/s13365-016-0472-1 · Cited by 50
“Microglia progenitors are thought to be of mesodermal/mesenchymal origin (Chan et al. 2007).”
BackgroundMicroglial precursors derived from mouse embryonic stem cells
Napoli, I., Kierdorf, K., & Neumann, H. (2009) · Glia · doi:10.1002/glia.20878 · Cited by 49
“The most widely accepted hypothesis is that microglia arise from the mesoderm and colonize the CNS in two waves at early embryonic and fetal development, although it is still questioned whether a subpopulation is derived from the neuroectoderm lineage (Chan et al., 2007).”
BackgroundNeurodevelopmental toxicity in the mouse neocortex following prenatal exposure to acetamiprid
Kagawa, N., & Nagao, T. (2018) · Journal of Applied Toxicology · doi:10.1002/jat.3692 · Cited by 49
Bilbo, S. D. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.02.017 · Cited by 46
“Microglial progenitor cells begin colonizing the rodent brain around embryonic day (E) 9-10 via the infiltration of primitive macrophage precursors from the yolk sac (Chan et al., 2007; Ginhoux et al., 2010).”
BackgroundPham, K., Luo, D., Liu, C., & Harrison, J. K. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.02.009 · Cited by 46
“Generally, thesemyeloidderived, macrophage-like microglial cells function as the main form of immune defense in the central nervous system (Gehrmann et al., 1995; Alliot et al., 1999; Streit, 2001; Chan et al., 2007; Rivest, 2009).”
Genetic approaches to study glial cells in the rodent brain
Pfrieger, F. W., & Ślęzak, M. (2011) · Glia · doi:10.1002/glia.22283 · Cited by 47
“Microglial cells are of mesodermal origin, but their ontogeny has been debated for quite some time (Chan et al., 2007; Prinz and Mildner, GLIA 2011).”
BackgroundTargeting innate immunity to protect and cure Alzheimer’s disease: opportunities and pitfalls
Cisbani, G., & Rivest, S. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01083-4 · Cited by 44
Retinal microglia polarization in diabetic retinopathy
Li, X., Yu, Z.-W., Li, H.-Y., Yuan, Y., Gao, X., & Kuang, H. (2021) · Visual Neuroscience · doi:10.1017/s0952523821000031 · Cited by 46
“Generally, as the macrophages of CNS, MG derives from hematopoietic stem cells (Chan et al., 2007; Saijo & Glass, 2011).”
BackgroundNeuroprotective effects of genistein in VSC4.1 motoneurons exposed to activated microglial cytokines
McDowell, M. L., Das, A., Smith, J. A., Varma, A. K., Ray, S. K., & Banik, N. L. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.04.011 · Cited by 44
“Microglia belong to the macrophage cell lineage and act as sensors during pathological events in the central nervous system (CNS) (Chan et al., 2007; Kreutzberg, 1996; Nakajima and Kohsaka, 2001).”
The behavior and functions of embryonic microglia
Hattori, Y. (2021) · Anatomical Science International · doi:10.1007/s12565-021-00631-w · Cited by 53
Monocyte-Derived Cells of the Brain and Malignant Gliomas: The Double Face of Janus
Kushchayev, S. V., Kushchayeva, Y. S., Wiener, P. C., Scheck, A. C., Badie, B., & Preul, M. C. (2012) · World Neurosurgery · doi:10.1016/j.wneu.2012.11.059 · Cited by 44
Microglia Cell Culture: A Primer for the Novice
Witting, A., & Möller, T. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-170-3_4 · Cited by 46
Nicotinic Acetylcholine Receptor Subunits in Rhesus Monkey Retina
Liu, J., McGlinn, A. M., Fernandes, A., Milam, A., Strang, C. E., Andison, M., Lindstrom, J., Keyser, K., & Stone, R. (2008) · Investigative Ophthalmology and Visual Science · doi:10.1167/iovs.08-2398 · Cited by 42
“Recent evidence indicates that microglia have a mesodermal origin, and thus a lineage distinct from that of macroglia that are derived from neuroectoderm.(53) In initial studies on human retina with a similar immunohistochemical approach (data not shown), antibodies to 4 and 7 nAChR subunits labeled various neuronal s…”
Yang, X., Zhang, Y., Chen, Y., He, X., Qian, Y., Xu, S., Gao, C., Mo, C., Chen, S., & Xiao, Q. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02267-z · Cited by 43
Life and death of microglia: Mechanisms governing microglial states and fates
Matsudaira, T., & Prinz, M. (2022) · Immunology Letters · doi:10.1016/j.imlet.2022.04.001 · Cited by 47
The role of microglial activation on ischemic stroke: Modulation by fibroblast growth factors
Dordoe, C., Huang, W., Bwalya, C., Wang, X., Shen, B., Wang, H., Wang, J., Ye, S., Wang, P., Xiaoyan, B., et al. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.07.005 · Cited by 44
Nuclear Receptors, Inflammation, and Neurodegenerative Diseases
Saijo, K., Crotti, A., & Glass, C. K. (2010) · Advances in immunology · doi:10.1016/s0065-2776(10)06002-5 · Cited by 42
Rapid isolation and culture of primary microglia from adult mouse spinal cord
Yip, P. K., Kaan, T. K. Y., Fenesan, D., & Malcangio, M. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.07.002 · Cited by 41
A Comparative Biology of Microglia Across Species
Sharma, K. P., Bisht, K., & Eyo, U. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.652748 · Cited by 46
Gaikwad, S., & Agrawal-Rajput, R. (2015) · International Journal of Inflammation · doi:10.1155/2015/361326 · Cited by 39
“Lipopolysaccharide from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs”
MethodSantambrogio, S., Ricca, A., Maderna, C., Ieraci, A., Aureli, M., Sonnino, S., Kulik, W., Aimar, P., Bonfanti, L., Martino, S., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds313 · Cited by 39
Arnold, T., & Betsholtz, C. (2013) · Vascular Cell · doi:10.1186/2045-824x-5-12 · Cited by 42
“It was previously thought that microglia arose from hematopoietic precursors in two waves of recruitment and differentiation [14,15].”
Meng, X., Chen, C.-L., Liu, Y., Su, S.-J., Gou, J., Huan, F.-N., Wang, D., Liu, H., Ben, S., & Lu, J. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.02.029 · Cited by 39
Neuroprotective function of microglia in the developing brain
Fujita, Y., & Yamashita, T. (2021) · Neuronal Signaling · doi:10.1042/ns20200024 · Cited by 37
Otsubo, Y., Satoh, Y., Kodama, M., Araki, Y., Satomoto, M., Sakamoto, E., Pagès, G., Pouysségur, J., Endo, S., & Kazama, T. (2012) · Pain · doi:10.1016/j.pain.2012.07.020 · Cited by 33
“The nestin promoter drives cre expression in neuronal and glial progenitors, but not in microglia, because microglia are of hematopoietic origin [5,12,14].”
BackgroundAPOE and immunity: Research highlights
Kloske, C. M., Barnum, C. J., Batista, A. F., Bradshaw, E. M., Brickman, A. M., Bu, G., Dennison, J. L., Gearon, M. D., Goate, A., Haass, C., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13020 · Cited by 38
“Neuroinflammation is a response of the innate immune system in the CNS which involves the activity of microglia and astrocytes in combination with their secreted cytokines, chemokines, and altered homeostatic functions, which together play a central role in an early phase of AD pathogenesis.”
Healing autism spectrum disorder with cannabinoids: a neuroinflammatory story
Carbone, E., Manduca, A., Cacchione, C., Vicari, S., & Trezza, V. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.12.009 · Cited by 38
Gu, W., Wang, Y., Qiu, Z., Dong, J., Wang, Y., & Chen, J. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.03.329 · Cited by 34
“In rodents represented by rats andmice, there is a developmental window (between embryonic days 10–19) during which mesenchymal origin microglial progenitors (a small portion of MG) populate the CNS (Chan et al., 2007).”
BackgroundYao, Y., & Tsirka, S. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.124891 · Cited by 35
Microglia and Their Promising Role in Ischemic Brain Injuries: An Update
Yu, L., Su, X., Li, S., Zhao, F., Mu, D., & Qu, Y. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00211 · Cited by 34
Characterization and isolation of immature neurons of the adult mouse piriform cortex
Rubio, A., Bellés, M., Belenguer, G., et al. (2015) · Developmental Neurobiology · doi:10.1002/dneu.22357 · Cited by 33
“5, n 5 3) and microglial cells were not labeled at all, suggesting that these cells were mostly generated during later developmental stages (Chan et al., 2007).”
BackgroundXavier, A. L. R., Lima, F. R. S., Nedergaard, M., & Menezes, J. R. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00037 · Cited by 33
“Monocytes precursors generated in the yolk sac invade the early embryonic nervous parenchyma as ameboid microglial cells (Chan et al., 2007; Ginhoux et al., 2010, 2013).”
BackgroundBeutner, C., Lepperhof, V., Dann, A., Linnartz‐Gerlach, B., Litwak, S. A., Napoli, I., Prinz, M., & Neumann, H. (2013) · Gene Therapy · doi:10.1038/gt.2012.100 · Cited by 32
Murgoci, A., Duhamel, M., Raffo‐Romero, A., Mallah, K., Aboulouard, S., Lefebvre, C., Kobeissy, F. H., Fournier, I., Žilková, M., Máderová, D., et al. (2020) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2020.1727637 · Cited by 32
“Recent studies have shown that the CNS hosts diverse populations of myeloid cells that include parenchymal microglia, macrophages and dendritic cells that are located in the leptomeninges, perivascular space and choroid plexus [1 – 3].”
The microglia-blood vessel interactions in the developing brain
Hattori, Y. (2022) · Neuroscience Research · doi:10.1016/j.neures.2022.09.006 · Cited by 37
The Development of Cannabinoid CBII Receptor Agonists for the Treatment of Central Neuropathies
Rivers‐Auty, J., & Ashton, J. C. (2010) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152410790780145 · Cited by 32
“Although still debated, it is commonly viewed that they are derived from mesodermal precursor cells of hematopoietic lineage, and that they enter the CNS during embryonic and early postnatal phases of development [28-30].”
BackgroundHerculano‐Houzel, S., & Santos, S. D. (2018) · Neuroglia · doi:10.3390/neuroglia1010014 · Cited by 30
Stem cell models of human synapse development and degeneration
Wilson, E. S., & Litwa, K. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-04-0222 · Cited by 30
Navone, N. D., Perga, S., Martire, S., Berchialla, P., Malucchi, S., & Bertolotto, A. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.04.017 · Cited by 31
“Furthermore, in the presence of inflammatory diseases of the central nervous system, bone marrowderived monocytes migrate into the brain and differentiate into microglia, the macrophages of the central nervous system (Chan et al., 2007).”
BackgroundChien, J.-Y., Chou, Y.-Y., Ciou, J.-W., Liu, F.-Y., & Huang, S. (2021) · Antioxidants · doi:10.3390/antiox10091466 · Cited by 31
“Resting microglia survey and maintain the microenvironment of the CNS, and under inflammatory conditions, these resting microglia convert into their activated form [14,15], express proinflammatory cytokines (including interleukin-1 (IL-1), IL-6, and nitric oxide (NO)), and produce oxidative stress, NFκB, and tumor nec…”
BackgroundMicroglial carbohydrate-binding receptors for neural repair
Linnartz‐Gerlach, B., Bodea, L., & Neumann, H. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1342-7 · Cited by 30
“the CNS by the yolk-sac-derived immature macrophages, microglial precursors positive for ionized calcium-binding adaptor molecule-1 (Iba1) locally proliferate within the CNS and mature to become adult microglia (Chan et al. 2007).”
BackgroundCell-replacement therapy and neural repair in the retina
Schmeer, C. W., Wohl, S. G., & Isenmann, S. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1335-6 · Cited by 30
Can Humanized Mice Reflect the Complex Pathobiology of HIV-Associated Neurocognitive Disorders?
Gorantla, S., Gendelman, H. E., & Poluektova, L. Y. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9335-y · Cited by 29
“The passive approaches to repopulate brain cells by transplantation of bone marrow or HSC in autologous mouse-to-mouse (Chan et al. 2007; Soulet and Rivest 2008), human-to-human (Cogle et al. 2004), or xenogeneic human-to-mouse (Asheuer et al. 2004) were not yet efficient .”
InfluentialWierda, R. J., Kuipers, H. F., van Eggermond, M. C. J. A., Benard, A., van Leeuwen, J. C., Carluccio, S., Geutskens, S. B., Jukema, J. W., Márquez, V. E., Quax, P. H. A., et al. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01482.x · Cited by 28
Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease
Fülöp, T., Tripathi, S., Rodrigues, S., Desroches, M., Bunt, T., Eiser, A. R., Bernier, F., Beauregard, P. B., Barron, A. E., Khalil, A., et al. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s264910 · Cited by 27
Neural inflammation and the microglial response in diabetic retinopathy
Abcouwer, S. F. (2011) · Journal of ocular biology, diseases, and informatics · doi:10.1007/s12177-012-9086-x · Cited by 27
“Although the developmental origins of microglia have been debated, it is widely accepted that they arise from hematopoietic stem cells [2, 3].”
BackgroundCarbone, E., Buzzelli, V., Manduca, A., Leone, S., Rava, A., & Trezza, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043920 · Cited by 25
Li, B., Gonzalez-Toledo, M. E., Piao, C.-S., Gu, A., Kelley, R. E., & Zhao, L.-R. (2011) · Alzheimer s Research & Therapy · doi:10.1186/alzrt67 · Cited by 26
“During development, the microglial progenitors, derived from mesenchymal myeloid linage progenitor cells, migrate into the embryonic brain before maturation of the blood-brain barrier [25].”
BackgroundWhat has single‐cell RNA sequencing revealed about microglial neuroimmunology?
Kubick, N., Flournoy, P. C. H., Klimovich, P., Manda, G., & Mickael, M. (2020) · Immunity Inflammation and Disease · doi:10.1002/iid3.362 · Cited by 27
Keswani, T., Roland, J., Herbert, F., Delcroix-Genête, D., Roy, H. B., Gaayeb, L., Cazenave, P., & Pied, S. (2019) · Genes and Immunity · doi:10.1038/s41435-019-0085-9 · Cited by 25
Metadata
- Authors
- Chan, W. Y., Kohsaka, S., & Rezaie, P.
- Affiliations
- Chinese University of Hong Kong (HK)
- National Institute of Neuroscience (JP)
- King's College London (GB)
- Venue
- Brain Research Reviews
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 53
- Issue
- 2
- Pages
- 344-354
- ISSN
- 0165-0173 (ISSN-L)
- OpenAlex
- W2087954391
- Cited by
- 400
- References
- 53
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 13 · 2022: 15 · 2021: 19 · 2020: 17 · 2019: 10 · 2018: 13 · 2017: 19 · 2016: 23 · 2015: 28 · 2014: 32 · 2013: 41 · 2012: 38
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Open Research Online - ORO (The Open University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- microglia, cell lineage, embryonic and fetal development, cell therapy, trophic factors, brain development, trophoblast
- MeSH terms
- Animals, Cell Differentiation, Humans, Models, Biological, Stem Cells, Microglia, Cell Lineage
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
