The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
A Combination of Ontogeny and CNS Environment Establishes Microglial Identity
Open accessAbstract
Microglia, the brain's resident macrophages, are dynamic CNS custodians with surprising origins in the extra-embryonic yolk sac. The consequences of their distinct ontogeny are unknown but critical to understanding and treating brain diseases. We created a brain macrophage transplantation system to disentangle how environment and ontogeny specify microglial identity. We find that donor cells extensively engraft in the CNS of microglia-deficient mice, and even after exposure to a cell culture environment, microglia fully regain their identity when returned to the CNS. Though transplanted macrophages from multiple tissues can express microglial genes in the brain, only those of yolk-sac origin fully attain microglial identity. Transplanted macrophages of inappropriate origin, including primary human cells in a humanized host, express disease-associated genes and specific ontogeny markers. Through brain macrophage transplantation, we discover new principles of microglial identity that have broad applications to the study of disease and development of myeloid cell therapies.
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“These genes are highly enriched in microglia and are not upregulated in monocytes that engraft the brain in microglia-depleted mouse models”
From Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program (2019) · cites this paper as Bennett et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, when macrophages enter the CNS, they adopt a microglia-like phenotype and express markers considered to be microglia-specific, further confounding analysis (Bennett et al., 2018).”
From Activated microglia drive demyelination via CSF1R signaling (2021) · cites this paper as Bennett et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Supporting this notion, once microglia are impaired by irradiation or genetic deficiencies, HSC-derived M F can efficiently and persistently colonize the brain parenchyma 14-17 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Experimentally seeded parenchymal brain MoM F were shown to retain epigenomes and expression signatures distinct from YSderived cells and respond differentially to challenges, even following prolonged brain residence 14-17 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [17]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“recent transplantation experiments suggest that Ms4a7 and other markers in Cluster 6 are specific to hematopoietic derived cells versus those derived from yolk-sac progenitors (Bennett et al., 2018).”
From Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain (2018) · cites this paper as Bennett et al., 2018
In the citing paper
“The loss of the homeostatic microglial gene P2ry12 (Bennett et al. , 2018) from the R6/2 striatum in our dataset (FDR 5 0.1, LogFC = -0.7083 versus control)”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Bennett et al. , 2018
In the citing paper
“This study shows that transplanted macrophages from multiple tissues can express microglial genes in the brain; however, only those of yolk sac origin fully attain microglial identity.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [220]
In the citing paper
“This study shows that transplanted macrophages from multiple tissues can express microglial genes in the brain; however, only those of yolk sac origin fully attain microglial identity.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [220]
In the citing paper
“Barres group recently identified Tmem119++/Sall1+/Gpr56+/Apoe+ as yolk sac-derived microglia, whereas hematopoietic stem cell-derived microglia-like cells express Tmem119+/Ms4a7+/Clec12a+/Apoe+++ suggesting lineage-specific microglia markers that can be useful in determining the origin of microglia [18, 19].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [18]
In the citing paper
“suggesting lineage-specific microglia markers that can be useful in determining the origin of microglia [18, 19].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [18]
In the citing paper
“Recent genomic and proteomic studies revealed microglia express a unique set of genes distinct from infiltrating monocytes and other immune cells [18, 19].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [18]
In the citing paper
“Barres group recently identified Tmem119++/Sall1+/Gpr56+/Apoe+ as yolk sac-derived microglia, whereas hematopoietic stem cell-derived microglia-like cells express Tmem119+/Ms4a7+/Clec12a+/Apoe+++ suggesting lineage-specific microglia markers that can be useful in determining the origin of microglia [18, 19].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [18]
In the citing paper
“It can be reversed by engraftment of isolated cells into brains lacking microglia, suggesting that additional CNS-specific cues are required to sustain microglia specification [18, 66].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [18]
In the citing paper
“It can be reversed by engraftment of isolated cells into brains lacking microglia, suggesting that additional CNS-specific cues are required to sustain microglia specification [18, 66].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [18]
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Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971
Self-citationFate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175
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“Sample-size estimations and method of computation Sample-size estimations for RNaseq experiments were empirically based on past studies (Clarke et al., 2018; Zhang et al., 2014).”
Self-citationMetsalu, T., & Vilo, J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv468 · Cited by 3,770
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979
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Microglia states and nomenclature: A field at its crossroads
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Microglial signatures and their role in health and disease
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Metadata
- Authors
- Bennett, F. C., Bennett, M. L., Yaqoob, F., Mulinyawe, S. B., Grant, G. A., Hayden Gephart, M., Plowey, E. D., & Barres, B. A.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Bennett, F. Chris
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 98
- Issue
- 6
- Pages
- 1170-1183.e8
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6023731
- OpenAlex
- W2807609377
- Cited by
- 524
- References
- 59
- Citations by year
- 2026: 44 · 2025: 59 · 2024: 47 · 2023: 67 · 2022: 73 · 2021: 77 · 2020: 75 · 2019: 57 · 2018: 24
- FWCI
- 26.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (S10RR025518-01, NS069375, P50AG047366, R37DA01504317)
- NRSA (F31 NS078813, T32MH019938-22, K08MH112120, K08NS901527, R01CA216054-01, K08 NS075144)
- JPB Foundation
- the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (853, 04-7023433)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- microglia, microglial reprogramming, disease-associated microglia, humanized mice, microglial markers
- MeSH terms
- Animals, Brain, Central Nervous System, Hematopoietic Stem Cells, Humans, Macrophages, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Microglia, Mice, Knockout, Cell Lineage, Mice
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