The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Origin, fate and dynamics of macrophages at central nervous system interfaces
Open accessAbstract
Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus, 4 weeks after TAM administration, recombination is largely restricted to microglia and other long-lived macrophages (e.g., perivascular macrophages) in Cx3cr1CreER mouse lines.15”
From A comparative analysis of microglial inducible Cre lines (2023) · cites this paper as [15]
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
“the Tmem119CreER, HexbCreER, and P2ry12CreER lines do not target border-associated macrophages in the CNS.15,20,21,30”
From A comparative analysis of microglial inducible Cre lines (2023) · cites this paper as [15]
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
“The yolk sac-derived precursors of resident macrophages are only in the perivascular compartment [360,361], where they maintain their cellular origin in adulthood [362,363,364].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [363]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Of note, using Cx3cr1 CreERT2 mice to delete microglial genes may also affect border-associated macrophages (BAMs) 16 , albeit to a lesser extent as BAMs were shown to be continuously replenished from skull bone marrow, unlike microglia 17 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Likewise, also parenchymal brain M F are thought to comprise during the life time of healthy mice exclusively YS-derived microglia and no MoM F 8-10 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [9]
In the citing paper
“Residing in the intracerebral perivascular space, delimited by the glia limitans and the vascular basement membrane (Virchow-Robin space), PVMs are closely apposed to the outer vessel wall and originate from hematopoietic precursors (18,20,21).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [18]
In the citing paper
“Based on current FACS and immunohistochemical analysis, the transcription factor SALL1 was identified as a key marker for microglia.”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [20]
In the citing paper
“Both microglia and BAMs are CD11b+/CD45low, making it difficult to distinguish between them without localization patterns.”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [20]
In the citing paper
“High expression of SALL1 in microglia allows distinguishing SALL1+ microglia from SALL1− BAM cells and infiltrating peripheral monocytes [20, 21].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [20]
In the citing paper
“In addition to microglia, new CD38+ resident myeloid cells called CNS border-associated macrophages (BAMs) are embryonically-derived cells that line along the meninges, choroid plexus, and perivascular spaces [20].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [20]
In the citing paper
“Moreover, single microglia nuclei-based analysis allowed us to exclude perivascular macrophages (Cx3cr1+, Tmem119-, and P2ry12-low)35 as potential factors driving the cbMg clearance-promoting gene expression signature.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [35]
In the citing paper
“Cx3cr1+ perivascular/meningeal macrophages were identified by low Tmem119, low Hexb, and high Mrc1 expression35,84 and excluded from single cell analysis (n=1-5 per plate).”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [35]
In the citing paper
“Like microglia, most macrophages residing in the leptomeninges and perivascular spaces are derived from early yolk sac–derived erythromyeloid progenitors, and during steady state, these cells have minimal turnover.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [71]
In the citing paper
“This contrasts with macrophages in the choroid plexus and dura mater, which do turn over and receive some input from peripheral blood monocytes during adulthood (71-73).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [71]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
Fate 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
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913
Self-citationFate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
Self-citationCell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124
Self-citationDevelopment of Monocytes, Macrophages, and Dendritic Cells
Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M., & Ley, K. (2010) · Science · doi:10.1126/science.1178331 · Cited by 3,049
Self-citationA Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578
Self-citationIdentification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., et al. (2015) · Nature · doi:10.1038/nature13989 · Cited by 2,339
Self-citationMonocytes and macrophages: developmental pathways and tissue homeostasis
Ginhoux, F., & Jung, S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3671 · Cited by 1,840
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–122 of 122
Role of P2X7 Receptors in Immune Responses During Neurodegeneration
Oliveira-Giacomelli, Á., Petiz, L. L., Andrejew, R., Turrini, N., Silva, J. B., Sack, U., & Ulrich, H. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.662935 · Cited by 68
Wahane, S., Zhou, X., Zhou, X., Guo, L., Friedl, M.-S., Kluge, M., Ramakrishnan, A., Shen, L., Friedel, C. C., Zhang, B., et al. (2021) · Science Advances · doi:10.1126/sciadv.abd8811 · Cited by 67
Wan, H., Brathwaite, S., Ai, J., Hynynen, K., & Macdonald, R. L. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20980296 · Cited by 65
Immunological defense of CNS barriers against infections
Ampie, L., & McGavern, D. B. (2022) · Immunity · doi:10.1016/j.immuni.2022.04.012 · Cited by 63
Scheckel, C., Imeri, M., Schwarz, P., & Aguzzi, A. (2020) · eLife · doi:10.7554/elife.62911 · Cited by 57
The niche matters: Origin, function and fate of CNS-associated macrophages during health and disease
Dalmau Gasull, A., Glavan, M., Samawar, S. K. R., Kapupara, K., Kelk, J., Rubio, M., Fumagalli, S., Sorokin, L., Vivien, D., & Prinz, M. (2024) · Acta Neuropathologica · doi:10.1007/s00401-023-02676-9 · Cited by 60
Self-citationSTOP floxing around: Specificity and leakiness of inducible Cre/loxP systems
Stifter, S. A., & Greter, M. (2020) · European Journal of Immunology · doi:10.1002/eji.202048546 · Cited by 48
Bedolla, A. M., McKinsey, G. L., Ware, K., Santander, N., Arnold, T. D., & Luo, Y. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113660 · Cited by 53
Uriarte Huarte, O., Kyriakis, D., Heurtaux, T., Pires-Afonso, Y., Grzyb, K., Halder, R., Buttini, M., Skupin, A., Mittelbronn, M., & Michelucci, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.639613 · Cited by 52
Mechanisms of myeloid cell entry to the healthy and diseased central nervous system
Amann, L., Masuda, T., & Prinz, M. (2023) · Nature Immunology · doi:10.1038/s41590-022-01415-8 · Cited by 50
Self-citationLopez‐Atalaya, J. P., Askew, K. E., Sierra, A., & Gomez‐Nicola, D. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22545 · Cited by 49
Kaufman-Francis, K., Djordjevic, J. T., Juillard, P.-G., Lev, S., Desmarini, D., Grau, G. E. R., & Sorrell, T. C. (2018) · The American Journal of Pathology · doi:10.1016/j.ajpath.2018.03.015 · Cited by 46
Redefining Microglial Identity in Health and Disease at Single-Cell Resolution
Provenzano, F., Pérez, M. J., & Deleidi, M. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.001 · Cited by 45
Zia, S., Hammond, B. P., Zirngibl, M., Sizov, A., Baaklini, C. S., Panda, S. P., Ho, M. F. S., Lee, K. V., Mainali, A., Burr, M. K., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00584-2 · Cited by 40
Kim, J.-S., Trzebanski, S., Shin, S.-H., Schori, L., Frumer Friedman, G. R., Ilani, N. C., Kadam, A., Vicario, R., Aust, O., Bugaeva, P., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115609 · Cited by 33
Self-citationMorsey, B., Niu, M., Dyavar, S. R., Fletcher, C. V., Lamberty, B. G., Emanuel, K., Fangmeier, A., & Fox, H. S. (2021) · iScience · doi:10.1016/j.isci.2021.102357 · Cited by 25
Bartalska, K., Hübschmann, V., Korkut-Demirbaş, M., Cubero, R. J. A., Venturino, A., Rössler, K., Czech, T., & Siegert, S. (2022) · iScience · doi:10.1016/j.isci.2022.104580 · Cited by 22
Impact of aging on meningeal gene expression
Neutzner, M., Kohler, C., Frank, S., Killer, H. E., & Neutzner, A. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00412-9 · Cited by 17
CNS macrophage contributions to myelin health
Hoffmann, A., & Miron, V. E. (2024) · Immunological Reviews · doi:10.1111/imr.13416 · Cited by 13
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11
The brain washing system in sepsis-associated encephalopathy
Chen, T., Hu, J., Liao, Y., Xie, S., & Zhang, L. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03602-4 · Cited by 8
Microglial states revisited: from homeostasis to disease
Eggen, B. J. L., & Kooistra, S. M. (2026) · Nature Reviews Neuroscience · doi:10.1038/s41583-026-01066-w · Cited by 6
Metadata
- Authors
- Goldmann, T., Wieghofer, P., Jordão, M. J. C., Prutek, F., Hagemeyer, N., Frenzel, K., Amann, L., Staszewski, O., Kierdorf, K., Krueger, M., Locatelli, G., Hochgerner, H., Zeiser, R., Epelman, S., Geissmann, F., Priller, J., Rossi, F. M. V., Bechmann, I., Kerschensteiner, M., Linnarsson, S., Jung, S., & Prinz, M.
- Affiliations
- University Medical Center Freiburg (DE)
- University of Freiburg (DE)
- Leipzig University (DE)
- Institut für Klinische Neuroimmunologie (DE)
- Karolinska Institutet (SE)
- University Health Network (CA)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- University of British Columbia (CA)
- Munich Cluster for Systems Neurology (DE)
- Weizmann Institute of Science (IL)
- Corresponding author
- Prinz, Marco
- ORCID
- Venue
- Nature Immunology
- Published
- 2016-05-02
- Volume
- 17
- Issue
- 7
- Pages
- 797-805
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4968048
- OpenAlex
- W2345745180
- Cited by
- 1,209
- References
- 52
- Citations by year
- 2026: 94 · 2025: 103 · 2024: 166 · 2023: 134 · 2022: 137 · 2021: 150 · 2020: 134 · 2019: 106 · 2018: 103 · 2017: 65 · 2016: 17
- FWCI
- 53.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- BORIS (University Library Bern) (submittedVersion)
- DZNE Pub (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- 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
- macrophage origin, choroid plexus macrophages, meningeal macrophages, perivascular macrophages, PU.1, parabiosis, macrophage turnover, central nervous system immunity, transcription factors
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Cell Differentiation, Cells, Cultured, Central Nervous System, Hematopoietic Stem Cells, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Fluorescence, Monocytes, Parabiosis, Proto-Oncogene Proteins, Trans-Activators, Microglia, Mice, Knockout, Mice
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
