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A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment
Open accessAbstract
While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in both the healthy and diseased brain.
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“Our consensus exAM signature does overlap with the dissociation signature in the study by Van Hove et al.[43] (19 of 25 genes in consensus exAM list; Supplementary Tables 4, 5 and 21a).”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as Van Hove et al.[43]
In the citing paper
“Consistent with the reports from other tissues in mice, we found that typical enzymatic digestion of mouse brain tissue induced a host of transcriptional alterations34,43,44,65.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [43]
In the citing paper
“However, emerging results from other tissues/cell types have begun to characterize dissociation artifacts following enzymatic digestion43–45,65,66.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [43]
In the citing paper
“No explicit statistical methods were used to predetermine sample sizes but our sample sizes exceed those reported in previous publications32,34,43.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [43]
In the citing paper
“This molecule likely also affects BAMs, as reported in the case of PLX3397 [317], placing an important caveat on the interpretation of data where PLX5622 is assumed to be purely microglia-specific.”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [317]
In the citing paper
“Although microglia represent a heterogeneous cell population [46], they still share several expression profiles with primitive and adult macrophages, including IBA1.”
From The Cuprizone Model: Dos and Do Nots (2020) · cites this paper as [46]
In the citing paper
“In the Aging Mouse Brain Single Cell Portal, Plcg2 expression is highest in microglia and brain macrophages, with lower levels in endothelial cells and oligodendrocyte precursor cells and minimal to no expression in neurons, astrocytes, and mature oligodendrocytes [30, 72–74].”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [74]
In the citing paper
“In the Brain Immune Atlas aggregate of CD45+ cells from brain and meningeal regions, Plcg2 transcripts are detected in 18% of immune cells across parenchymal microglia and multiple border-associated macrophage (BAM) subsets, with choroid plexus surface and dural BAMs contributing many Plcg2+ cells and a small B-cell cluster displaying the highest per-cell Plcg2 expression in the dataset [74].”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [74]
In the citing paper
“We identified a classical monocyte cluster that highly express Ly6c2, and a non-classical monocyte cluster highly express Itgal, similarly as a published single cell RNA-seq study.88”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [88]
In the citing paper
“In addition, we confirmed previous findings of elevated expression of lipid-related genes in BAMs (31) and observed an increase in LD content within these cells over time and during disease progression.”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [31]
In the citing paper
“MHCII+ macrophages are most abundant in the choroid plexus and meninges [37], and we similarly observe widespread uptake of L2-siRNA in this population (Fig. 5F).”
From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [37]
In the citing paper
“MHCII+ macrophages are most abundant in the choroid plexus and meninges,43 and we similarly observe widespread uptake of L2-siRNA in this population (Fig. 5F).”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [43]
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 [364]
In the citing paper
“As immune surveillants, CAMs clear harmful substances through phagocytosis, antigen presentation, and cytokine production [364,368,371,372,373,374,375,376]”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [364]
In the citing paper
“CD38 expression was associated with neuroinflammation with greater amounts of proinflammatory macrophages/microglia in mouse brains160,165.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [165]
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 [73]
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 [73]
In the citing paper
“On the basis of high-parameter mass cytometry and single-cell RNA-sequencing studies, the dural macrophages appear to be distinct from those residing in the pia and underlying parenchyma (73, 94).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [73]
In the citing paper
“The macrophages expressed markers of border associated macrophages (BAMs) (e.g., Apoe, Ms4a7, Ms4a6c) recently identified in periluminal regions, meninges, and ChP (Van Hove et al., 2019).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Van Hove et al., 2019
In the citing paper
“Similarly, we found a subset of macrophages expressing markers previously defined as subdural-specific BAMs (e.g., Lyve1, Ednrb, Colec12; Van Hove et al., 2019) that were enriched in embryonic ChP macrophages in our dataset (Figure S5H).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Van Hove et al., 2019
In the citing paper
“However, in contrast to Van Hove et al., our data revealed that this separation was age-dependent and potentially represented a maturation-dependent shift from MHC IIlow to MHC IIhigh (Figure 5I, S5I,J, Table S6).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Van Hove et al., 2019
In the citing paper
“In agreement with recent reports (Van Hove et al., 2019), we found diversity within the BAMs, which segregated into two subsets defined as major histocompatibility complex (MHC) class IIlow and MHC IIhigh.”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Van Hove et al., 2019
In the citing paper
“These maturation dependent changes agree with a recent report of BAMs (Van Hove et al., 2019).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Van Hove et al., 2019
Citations
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
Scenic: single-cell regulatory network inference and clustering.
Aibar, S., González-Blas, C. B., Moerman, T., Huynh-Thu, V. A., Imrichova, H., Hulselmans, G., Rambow, F., Marine, J.-C., Geurts, P., Aerts, J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4463 · Cited by 6,520
Self-citationlimma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
Structural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413
Cited by
Sorted by citations
Items 101–200 of 982
Hypertension, Neurodegeneration, and Cognitive Decline
Pacholko, A. G., & Iadecola, C. (2024) · Hypertension · doi:10.1161/hypertensionaha.123.21356 · Cited by 170
“…of intracerebral arterioles and venules within the PVS. 81 PVM express both AT1R and IL-17RA, are richly endowed with the reactive oxygen species producing enzyme NOX2, 100,101 and have emerged as key players in the neurovascular and cognitive dysfunction observed in animal models of hypertension.”
BackgroundSingle Cell RNA Sequencing in Atherosclerosis Research
Williams, J. W., Winkels, H., Durant, C. P., Zaitsev, K., Ghosheh, Y., & Ley, K. F. (2020) · Circulation Research · doi:10.1161/circresaha.119.315940 · Cited by 142
Han, B., Zhou, S., Zhang, Y., Chen, S., Xi, W., Liu, C., Zhou, X., Yuan, M., Yu, X., Li, L., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adg1323 · Cited by 143
Earls, R. H., Menees, K. B., Chung, J., Gutekunst, C., Lee, H. J., Hazim, M. G., Rada, B., Wood, L. B., & Lee, J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909110117 · Cited by 146
“Our findings compliment recent transcriptomic analyses demonstrating the diversity of immune cells in the brain and that NK cells are one of the distinct populations within the brain along with B cells, T cells, and dendritic cells in both homeostatic and disease statuses (39, 40).”
BackgroundResultChen, H.-R., Sun, Y.-Y., Chen, C.-W., Kuo, Y.-M., Kuan, I. S., Tiger Li, Z.-R., Short-Miller, J. C., Smucker, M. R., & Kuan, C.-Y. (2020) · Science Advances · doi:10.1126/sciadv.abb2119 · Cited by 140
Kim, S., Lee, W., Jo, H., Sonn, S., Jeong, S., Seo, S., Suh, J., Jin, J., Kweon, H. Y., Kim, T. K., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102347 · Cited by 140
Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies
Benmamar-Badel, A., Owens, T., & Wlodarczyk, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00430 · Cited by 124
“This population named “Kolmer’s epiplexus cells” closely resembles microglial cells and was associated with enriched expression of Spp1, Apoe, and Igf1 (82).”
BackgroundBrain macrophage development, diversity and dysregulation in health and disease
Silvin, A., Qian, J., & Ginhoux, F. (2023) · Cellular & Molecular Immunology · doi:10.1038/s41423-023-01053-6 · Cited by 137
“2) [18, 20, 24].”
BackgroundMethodInfluentialInflammatory aspects of Alzheimer’s disease
Lucena, P. B., & Heneka, M. T. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02790-2 · Cited by 152
“Also, several subgroups of BAMs have been identified based on their anatomical site: subdural/leptomeningeal macrophages (sdΜΦ), dural macrophages (dmΜΦ), stromal choroid plexus macrophages (cpΜΦ), choroid epiplexus macrophages (cp epi ΜΦ), and perivascular macrophages (PVMs) [236].”
Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease
Derk, J., Jones, H. E., Como, C., Pawlikowski, B., & Siegenthaler, J. A. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703944 · Cited by 120
The choroid plexus: a missing link in our understanding of brain development and function
Saunders, N. R., Dzięgielewska, K. M., Fame, R. M., Lehtinen, M. K., & Liddelow, S. A. (2022) · Physiological Reviews · doi:10.1152/physrev.00060.2021 · Cited by 145
Phenotypic impacts of CSF1R deficiencies in humans and model organisms
Hume, D. A., Caruso, M., Ferrari-Cestari, M., SUMMERS, K. M., Pridans, C., & Irvine, K. M. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0519-143r · Cited by 125
The influence of environment and origin on brain resident macrophages and implications for therapy
Bennett, M. L., & Bennett, F. C. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0545-6 · Cited by 136
Wang, Y., Chen, D., Xu, D., Huang, C., Xing, R., He, D., & Xu, H. (2021) · Immunity · doi:10.1016/j.immuni.2021.09.016 · Cited by 132
Chiot, A., Zaïdi, S., Iltis, C., Ribon, M., Berriat, F., Schiaffino, L., Jolly, A., de la Grange, P., Mallat, M., Bohl, D., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00718-z · Cited by 122
Microglia in neurodegenerative diseases
Xu, Y., Jin, M.-Z., Yang, Z., & Jin, M.-Z. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290881 · Cited by 121
Spinal macrophages resolve nociceptive hypersensitivity after peripheral injury
Niehaus, J. K., Taylor‐Blake, B., Loo, L., Simon, J. M., & Zylka, M. J. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.018 · Cited by 125
SUMMERS, K. M., Bush, S. J., & Hume, D. A. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000859 · Cited by 114
“Cluster 41 contains numerous immediate early genes (IEGs) encoding transcription factors and feedback regulators (for example, Fos , Egr1 , and Dusp1 ), consistent with evidence from scRNA-seq of disaggregated cells that isolation of cells from tissues produces cell activation [59, 146].”
Stroke induces disease-specific myeloid cells in the brain parenchyma and pia
Beuker, C., Schafflick, D., Strecker, J., Heming, M., Li, X., Wolbert, J., Schmidt‐Pogoda, A., Thomas, C., Kuhlmann, T., Aranda-Pardos, I., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28593-1 · Cited by 126
Microglial Corpse Clearance: Lessons From Macrophages
Márquez-Ropero, M., Benito, E., Plaza‐Zabala, A., & Sierra, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00506 · Cited by 115
“Similar observations are being made in other macrophage populations, with singlecell omics techniques revealing their underlying richness and diversity (49, 50).”
Grabert, K., Sehgal, A., Irvine, K. M., Wollscheid-Lengeling, E., Ozdemir, D. D., Stables, J., Luke, G. A., Ryan, M. D., Adamson, A., Humphreys, N. E., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000835 · Cited by 114
Shipley, F. B., Dani, N., Xu, H., Deister, C., Cui, J., Head, J. P., Sadegh, C., Fame, R. M., Shannon, M. L., Flores, V. I., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.024 · Cited by 118
Meningeal macrophages protect against viral neuroinfection
Rebejac, J., Eme‐Scolan, E., Arnaud, L., Kharbouche, S., Teleman, M., Spinelli, L., Gallo, E., Roussel‐Queval, A., Zarubica, A., Sansoni, A., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.005 · Cited by 116
Skull bone marrow channels as immune gateways to the central nervous system
Mazzitelli, J. A., Pulous, F. E., Smyth, L. C. D., Kaya, Z., Rustenhoven, J., Moskowitz, M. A., Kipnis, J., & Nahrendorf, M. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01487-1 · Cited by 116
“4.”
The pathogenesis of cerebral small vessel disease and vascular cognitive impairment
Markus, H. S., & Joutel, A. (2025) · Physiological Reviews · doi:10.1152/physrev.00028.2024 · Cited by 140
Meningeal Lymphatics: From Anatomy to Central Nervous System Immune Surveillance
Papadopoulos, Z., Herz, J., & Kipnis, J. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900838 · Cited by 114
“conventional DC2s (28), including a subpopulation of migratory (CCR7-expressing) DCs.”
BackgroundMacrophages on the margin: choroid plexus immune responses
Cui, J., Xu, H., & Lehtinen, M. K. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.07.002 · Cited by 117
Activity-dependent modulation of synapse-regulating genes in astrocytes
Farhy-Tselnicker, I., Boisvert, M., Liu, H., Dowling, C. C., Erikson, G. A., Blanco‐Suárez, E., Farhy, C., Shokhirev, M. N., Ecker, J. R., & Allen, N. J. (2021) · eLife · doi:10.7554/elife.70514 · Cited by 108
Current Knowledge of Microglia in Traumatic Spinal Cord Injury
Xu, L., Wang, J., Ding, Y., Wang, L., & Zhu, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.796704 · Cited by 112
“Microglia is the only resident phagocyte in the parenchyma in the steady-state (10, 22), but microglia is easily confused withmacrophages outside parenchyma termed border-associated macrophages (BAMs) which reside in the perivascular space, meninges, and choroid plexus (13, 23) (Figure 1).”
BackgroundThe choroid plexus and its role in the pathogenesis of neurological infections
Thompson, D., Brissette, C. A., & Watt, J. A. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00372-6 · Cited by 116
Distinct roles of the meningeal layers in CNS autoimmunity
Merlini, A., Haberl, M., Strauß, J., Hildebrand, L., Genc, N., Franz, J., Chilov, D., Alitalo, K. K., Flügel‐Koch, C., Stadelmann, C., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01108-3 · Cited by 110
The CNS Immune Landscape from the Viewpoint of a T Cell
Mundt, S., Greter, M., Flügel, A., & Becher, B. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.07.008 · Cited by 107
Wang, A. Z., Bowman-Kirigin, J. A., Desai, R. R., Kang, L., Patel, P. R., Patel, B., Khan, S. M., Bender, D. E., Marlin, M. C., Liu, J., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01051-9 · Cited by 111
Rajan, W. D., Wojtaś, B., Gielniewski, B., Miró‐Mur, F., Pedragosa, J., Zawadzka, M., Pilanc, P., Planas, A. M., & Kaminska, B. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104722 · Cited by 106
Microglia in brain development and regeneration
Mehl, L. C., Manjally, A. V., Bouadi, O., Gibson, E. M., & Tay, T. L. (2022) · Development · doi:10.1242/dev.200425 · Cited by 113
Border-associated macrophages in the central nervous system
Sun, R., & Jiang, H. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03059-x · Cited by 120
Resident tissue macrophages: Key coordinators of tissue homeostasis beyond immunity
Zhao, J., Andreev, I., & Silva, H. M. (2024) · Science Immunology · doi:10.1126/sciimmunol.add1967 · Cited by 109
“These cells have previously been called parenchymal border macrophages ( 28 , 52 , 55 ), border-associated macrophages ( 41 , 51 , 52 , 56 ), or central nervous system–associated macrophages ( 17 , 39 , 53 ).”
Age-related alterations in meningeal immunity drive impaired CNS lymphatic drainage
Rustenhoven, J., Pavlou, G., Storck, S. E., Dykstra, T., Du, S., Wan, Z., Quintero, D., Scallan, J. P., Smirnov, I., Kamm, R. D., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20221929 · Cited by 108
Brain perivascular macrophages: Recent advances and implications in health and diseases
Yang, T., Guo, R., & Zhang, F. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13263 · Cited by 97
Single-cell isoform analysis in human immune cells
Volden, R., & Vollmers, C. (2022) · Genome biology · doi:10.1186/s13059-022-02615-z · Cited by 85
Macrophage profiling in atherosclerosis: understanding the unstable plaque
Gianopoulos, I., & Daskalopoulou, S. S. (2024) · Basic Research in Cardiology · doi:10.1007/s00395-023-01023-z · Cited by 101
“Tissue digestion protocols also induce cell stress signatures [162, 165], which can be avoided by adding transcriptional inhibitors during single-cell suspension processing [28].”
Brain perivascular macrophages: current understanding and future prospects
Wen, W., Cheng, J., & Tang, Y. (2023) · Brain · doi:10.1093/brain/awad304 · Cited by 107
Stratoulias, V., Ruiz, R., Kanatani, S., Osman, A. M., Keane, L., Armengol, J. A., Rodríguez-Moreno, A., Murgoci, A.-N., García-Domínguez, I., Alonso-Bellido, I., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01326-3 · Cited by 96
Immune dynamics in the CNS and its barriers during homeostasis and disease*
Buckley, M. W., & McGavern, D. B. (2022) · Immunological Reviews · doi:10.1111/imr.13066 · Cited by 107
Translational opportunities of single-cell biology in atherosclerosis
de Winther, M. P. J., Bäck, M., Evans, P. C., Gomez, D. A., Gonçalves, I., Jørgensen, H. F., Koenen, R. R., Lutgens, E., Norata, G. D., Osto, E., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac686 · Cited by 97
IL4i1 and IDO1: Oxidases that control a tryptophan metabolic nexus in cancer
Zeitler, L., & Murray, P. J. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104827 · Cited by 100
“Ccl22, Ccr7, Fscn1, Il4i1, Il12b, Nudt17, Socs2, Tnfrsf4 (52)”
Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair
De Ponti, F. F., Bujko, A., Liu, Z., Collins, P. J., Schuermans, S., Maueroder, C., Amstelveen, S., Thoné, T., Martens, L., McKendrick, J. G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.01.002 · Cited by 94
Self-citationMicroenvironmental Heterogeneity in Brain Malignancies
Perus, L. J. M., & Walsh, L. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02294 · Cited by 96
The role of natural killer cells in Parkinson’s disease
Earls, R. H., & Lee, J. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00505-7 · Cited by 94
Ostkamp, P., Deffner, M., Schulte‐Mecklenbeck, A., Wünsch, C., Lu, I., Wu, G. F., Goelz, S. E., Jager, P. L. D., Kuhlmann, T., Groß, C. C., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.adc9778 · Cited by 93
The contribution of the peripheral immune system to neurodegeneration
Berriat, F., Lobsiger, C. S., & Boillée, S. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01323-6 · Cited by 87
White matter microglia heterogeneity in the CNS
Amor, S., McNamara, N. B., Gerrits, E., Marzin, M. C., Kooistra, S. M., Miron, V. E., & Nutma, E. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02389-x · Cited by 89
“However, these proteins are not unique to microglia as other macrophage populations, such as infiltrating monocytederived macrophages present during neuroinflammation and CNS-associated macrophages (CAMs), have also been reported to express these markers [6, 64, 98, 142].”
BackgroundJahromi, N. H., Marchetti, L., Moalli, F., Duc, D., Basso, C., Tardent, H., Kaba, E., Deutsch, U., Pot, C., Sallusto, F., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03056 · Cited by 93
“Compensatory upregulation of other reported LFA-1 ligands, such as ICAM-3, ICAM-4, and ICAM-5 was not investigated as these molecules are not expressed in mouse myeloid cells and endothelial cells (56, 57).”
BackgroundMicroglia Diversity in Healthy and Diseased Brain: Insights from Single-Cell Omics
Ochocka, N., & Kaminska, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063027 · Cited by 97
Origin and Differentiation of Nerve-Associated Macrophages
Kolter, J., Kierdorf, K., & Henneke, P. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901077 · Cited by 91
Santisteban, M. M., Schaeffer, S. M., Anfray, A., Faraco, G., Brea, D., Wang, G., Sobanko, M., Sciortino, R. K., Racchumi, G., Waisman, A., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01497-z · Cited by 93
“Therefore, we used CD36 as a marker of BAMs, as shown by single-cell RNA sequencing data 35 .”
Meningeal Mechanisms and the Migraine Connection
Levy, D., & Moskowitz, M. A. (2023) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080422-105509 · Cited by 90
The old guard: Age-related changes in microglia and their consequences
Costa, J., Martins, S., Ferreira, P. A., Cardoso, A. M., Guedes, J. R., Peça, J., & Cardoso, A. L. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111512 · Cited by 88
CNS macrophages differentially rely on an intronic Csf1r enhancer for their development
Munro, D. A. D., Bradford, B. M., Mariani, S. A., Hampton, D. W., Vink, C. S., Chandran, S., Hume, D. A., Pridans, C., & Priller, J. (2020) · Development · doi:10.1242/dev.194449 · Cited by 85
Nicheformer: a foundation model for single-cell and spatial omics
Tejada-Lapuerta, A., Schaar, A. C., Gutgesell, R., Palla, G., Halle, L., Minaeva, M., Vornholz, L., Dony, L., Drummer, F., Richter, T., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02814-z · Cited by 100
Bypassing the blood-brain barrier
Rustenhoven, J., & Kipnis, J. (2019) · Science · doi:10.1126/science.aay0479 · Cited by 82
The Gut Microbiome as a Regulator of the Neuroimmune Landscape
Yu, L. W., Agirman, G., & Hsiao, E. Y. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-014237 · Cited by 75
Immunology in the Era of Single-Cell Technologies
Efremova, M., Vento‐Tormo, R., Park, J.-E., Teichmann, S. A., & James, K. R. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090419-020340 · Cited by 80
Askenase, M. H., Goods, B. A., Beatty, H. E., Steinschneider, A. F., Velazquez, S. E., Osherov, A., Landreneau, M. J., Carroll, S. L., Tran, T. B., Avram, V., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abd6279 · Cited by 82
Origin and Heterogeneity of Tissue Myeloid Cells: A Focus on GMP-Derived Monocytes and Neutrophils
Ng, L. G., Liu, Z., Kwok, I., & Ginhoux, F. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-081022-113627 · Cited by 91
Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis
Whiteley, A. E., Ma, D., Wang, L., Yu, S., Yin, C., Price, T. T., Simon, B. G., Xu, K. R., Marsh, K. A., Brockman, M. L., et al. (2024) · Science · doi:10.1126/science.adh5548 · Cited by 92
“Thisrevealedthat border-associatedmacrophages(BAMs),in-cludingsubdural,duralMHCII low , and dural MHCII high BAMs ( 35 ), and monocyte-derived macrophages (MDMs) were the predominant source of GDNF, whereas other meningeal cell populations, including monocytes, neutrophils, lymphocytes, natural…”
BackgroundAdvances and controversies in meningeal biology
Betsholtz, C., Engelhardt, B., Koh, G. Y., McDonald, D. M., Proulx, S. T., & Siegenthaler, J. A. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01701-8 · Cited by 91
“Dural macrophages are distinct from borderassociated macrophages in the SAS, as demonstrated by scRNAseq analysis and immunophenotyping 12,22,23 , consistent with meningeal layerspecific functions of these mac rophages.”
Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease
Kimura, K., Subramanian, A., Yin, Z., Khalilnezhad, A., Wu, Y., He, D., Dixon, K. O., Chitta, U. K., Ding, X., Adhikari, N., et al. (2025) · Nature · doi:10.1038/s41586-025-08852-z · Cited by 85
Meningeal lymphatic drainage: novel insights into central nervous system disease
Zhang, Q., Niu, Y., Li, Y., Xia, C., Chen, Z., Chen, Y., & Feng, H. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02177-z · Cited by 100
Unique aspects of IFN ‐γ/ STAT1 signaling in neurons
Clark, D. N., Begg, L. R., & Filiano, A. J. (2022) · Immunological Reviews · doi:10.1111/imr.13092 · Cited by 82
The role of neutrophils in the dysfunction of central nervous system barriers
Santos-Lima, B., Pietronigro, E. C., Terrabuio, E., Zenaro, E., & Constantin, G. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.965169 · Cited by 82
Lee, S.-H., Rezzonico, M. G., Friedman, B. A., Huntley, M. H., Meilandt, W. J., Pandey, S., Chen, Y.-J. J., Easton, A. E., Modrusan, Z. D., Hansen, D. V., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110158 · Cited by 82
The meningeal transcriptional response to traumatic brain injury and aging
Bolte, A. C., Shapiro, D. A., Dutta, A. B., Feng, W., Bruch, K. R., Kovacs, M. A., Marco, A. R., Ennerfelt, H. E., & Lukens, J. R. (2022) · eLife · doi:10.7554/elife.81154 · Cited by 78
Basal lamina changes in neurodegenerative disorders
Nguyen, B., Bix, G., & Yao, Y. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00502-y · Cited by 75
How microbiota shape microglial phenotypes and epigenetics
Erny, D., & Prinz, M. (2020) · Glia · doi:10.1002/glia.23822 · Cited by 80
“Additionally, bacteria produce different putative neurotransmitter precursors such as tryptophan (Yano et al., 2015) and gut bacteria are considered to be the main producers of SCFAs (acetate, propionate, butyrate) which are reported to be taken up many tissues and cells including the brain (Dalile, Van Oudenhove, Ver…”
BackgroundInfluentialRedefining CNS immune privilege
Smyth, L. C. D., & Kipnis, J. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-025-01175-0 · Cited by 80
“As a result, the dura mater has an immune composition that resembles an immunological barrier tissue, hosting diverse resident and patrolling immune cell populations 20,34 .”
InfluentialDiversity and function of brain-associated macrophages
Mildenberger, W., Stifter, S. A., & Greter, M. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102181 · Cited by 81
Brioschi, S., Belk, J. A., Peng, V., Molgora, M., Rodrigues, P. F., Nguyen, K. M., Wang, S., Du, S., Wang, W.-L., Grajales‐Reyes, G. E., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.028 · Cited by 86
Macrophage heterogeneity in the single-cell era: facts and artifacts
Hume, D. A., Millard, S. M., & Pettit, A. R. (2023) · Blood · doi:10.1182/blood.2023020597 · Cited by 83
The CD33 short isoform is a gain-of-function variant that enhances Aβ1–42 phagocytosis in microglia
Bhattacherjee, A., Jung, J., Zia, S., Ho, M. F. S., Eskandari‐Sedighi, G., Laurent, C. D. S., McCord, K. A., Bains, A., Sidhu, G., Sarkar, S., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00443-6 · Cited by 77
“We identified twelve clusters in total: ten microglial cell clusters, one cluster of border associated microglia (BAM – Cluster 9) [37], and one monocyte cluster (Cluster 11); these latter two clusters may represent cells of the leptomeningeal, perivascular, or choroid plexus tissue from brain isolation.”
BackgroundDissecting the human leptomeninges at single-cell resolution
Kearns, N. A., Iatrou, A., Flood, D. J., De Tissera, S., Mullaney, Z. M., Xu, J., Gaiteri, C., Bennett, D. A., & Wang, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-42825-y · Cited by 75
“Notably, the BAM markers LYVE1 and CD163 have previously been reported to distinguish leptomeningeal BAMs in mice 12,22 .”
InfluentialBeneficial and detrimental functions of microglia during viral encephalitis
Waltl, I., & Kalinke, U. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.11.004 · Cited by 74
“In recent years, single-cell RNA sequencing (scRNA-seq) provided deeper insight into the transcriptomic profiles of microglia [11,12,18,23].”
BackgroundCNS border-associated macrophages in the homeostatic and ischaemic brain
Gerganova, G., Riddell, A., & Miller, A. A. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108220 · Cited by 72
Masanetz, R. K., Winkler, J., Winner, B., Günther, C., & Süß, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911111 · Cited by 80
“The meninges, covering the CNS surface, are divided into the leptomeninges (pia mater and arachnoidea mater) and the dura mater, both of which contain resident macrophage populations as well as diverse other immune cells under homeostasis [95].”
BackgroundCadiz, M. P., Jensen, T. D., Sens, J. P., Zhu, K., Song, W.-M., Zhang, B., Ebbert, M., Chang, R., & Fryer, J. D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00531-1 · Cited by 73
X-chromosome regulation and sex differences in brain anatomy
Raznahan, A., & Distèche, C. M. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.10.024 · Cited by 69
Yang, J.-X., Wang, H., Chen, J.-Z., Li, H., Hu, J.-C., Yu, A.-A., Wen, J., Chen, S., Lai, W.-D., Wang, S., et al. (2022) · Frontiers in Pain Research · doi:10.3389/fpain.2022.946846 · Cited by 82
Border-associated macrophages as gatekeepers of brain homeostasis and immunity
Vara‐Pérez, M., & Movahedi, K. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.005 · Cited by 84
Self-citationMicroglia promote remyelination independent of their role in clearing myelin debris
Baaklini, C. S., Ho, M. F. S., Lange, T., Hammond, B. P., Panda, S. P., Zirngibl, M., Zia, S., Himmelsbach, K., Rana, H., Phillips, B., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113574 · Cited by 73
c-MAF–dependent perivascular macrophages regulate diet-induced metabolic syndrome
Silva, H. M., Kitoko, J. Z., Queiroz, C. P., Kroehling, L., Matheis, F., Yang, K. L., Reis, B. S., Ren‐Fielding, C. J., Littman, D. R., Bozza, M. T., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abg7506 · Cited by 75
Monocyte-neutrophil entanglement in glioblastoma
Friedmann‐Morvinski, D., & Hambardzumyan, D. (2023) · Journal of Clinical Investigation · doi:10.1172/jci163451 · Cited by 71
Lodder, C., Scheyltjens, I., Stancu, I., Lucena, P. B., de Ravé, M. G., Vanherle, S., Vanmierlo, T., Cremers, N., Vanrusselt, H., Brône, B., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01204-8 · Cited by 71
“Single-cell analysis first revealed the existence of DAMs in mouse amyloid models [29, 30, 65].”
BackgroundMethodInfluentialSelf-citationCurrent views on meningeal lymphatics and immunity in aging and Alzheimer’s disease
Rego, S., Sánchez, G., & Mesquita, S. D. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00645-0 · Cited by 79
“…in mice, the transcriptional signatures of microglia and of meningeal macrophages and brain PVMs (jointly called border-associated macrophages; BAMs) become distinct at embryonic day 12.5, mostly due to unparal-leled molecular cues present at the different anatomical locations [38, 45].”
BackgroundInfluentialMacrophage Responses to Environmental Stimuli During Homeostasis and Disease
Rasheed, A., & Rayner, K. J. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab004 · Cited by 83
Benhar, I., Ding, J., Yan, W., Whitney, I. E., Jacobi, A., Sud, M., Burgin, G., Shekhar, K., Tran, N. M., Wang, C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01437-w · Cited by 69
“5a) and lower levels of a microglia signature (Bennett et al., 2018; Hohsfield et al., 2020; Jordão et al., 2019; O’Koren et al., 2019; Shemer et al., 2018; Van Hove et al., 2019).”
BackgroundInfluentialMapunda, J. A., Pareja, J. R., Vladymyrov, M., Bouillet, E., Hélie, P., Pleskač, P., Barcos, S., Andræ, J., Vestweber, D., McDonald, D. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41580-4 · Cited by 72
Brain Parenchymal and Extraparenchymal Macrophages in Development, Homeostasis, and Disease
Brioschi, S., Zhou, Y., & Colonna, M. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900821 · Cited by 67
“Like microglia, BAMs are dependent on CSF1R signaling for their survival (74, 77).”
BackgroundInfluentialMicroglia Diversity in Health and Multiple Sclerosis
Zia, S., Rawji, K. S., Michaels, N. J., Burr, M. K., Kerr, B. J., Healy, L. M., & Plemel, J. R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.588021 · Cited by 70
Cotechini, T., Atallah, A., & Grossman, A. (2021) · Cells · doi:10.3390/cells10040960 · Cited by 74
“Moreover, alveolar macrophages, cardiac macrophages, F4/80+ brain microglia and barrier-associated macrophages in the brain can be replenished by circulating monocytes following age- or inflammation-associated cellular loss [28,32,33].”
BackgroundCNS Border-Associated Macrophages: Ontogeny and Potential Implication in Disease
Dermitzakis, I., Theotokis, P., Evangelidis, P., Delilampou, E., Evangelidis, N., Chatzisavvidou, A., Avramidou, E., & Μanthou, M. E. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45050272 · Cited by 74
“, cpM Φ remained unaltered in a study with Irf8 -deficient mice [8], while other research considered IRF8 as a regulator of cpM Φ maturation since the gene ablation suppressed the transcriptional programme of cpM Φ [14,53].”
BackgroundResultInfluential
Metadata
- Authors
- Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., Aerts, J., Berx, G., Boeckxstaens, G. E., Vandenbroucke, R. E., Vereecke, L., Moechars, D., Guilliams, M., Van Ginderachter, J. A., Saeys, Y., & Movahedi, K.
- Affiliations
- Ghent University (BE)
- Vrije Universiteit Brussel (BE)
- Janssen (Belgium) (BE)
- KU Leuven (BE)
- Ghent University Hospital (BE)
- Corresponding author
- Movahedi, Kiavash
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2019-05-06
- Volume
- 22
- Issue
- 6
- Pages
- 1021-1035
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2943220296
- Cited by
- 1,074
- References
- 68
- Citations by year
- 2026: 160 · 2025: 156 · 2024: 187 · 2023: 152 · 2022: 148 · 2021: 151 · 2020: 90 · 2019: 29
- FWCI
- 46.98
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Lirias (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain macrophages, border-associated macrophages, choroid plexus, dura mater, microglia, IRF8, macrophage ontogeny, postnatal brain development, self-renewal, cerebrospinal fluid
- MeSH terms
- Interferon Regulatory Factor-8, Animals, Brain, Cell Differentiation, Female, Macrophages, Male, Mice, Inbred C57BL, Microglia, Cell Lineage, Interferon Regulatory Factors, Mice
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