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.
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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
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Background
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
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