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A molecular atlas of cell types and zonation in the brain vasculature
Open accessAbstract
Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.
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In the citing paper
“many of which were well documented61–66.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [64]
In the citing paper
“We identified endothelial ICs (Figure 2E) with strong contributions from genes with arterial (IC 5 and 20) and veinous (IC 3 and 12) expression, suggesting heterogeneity related to vessel type”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“These genes (e.g. Tm4sf1 and Slc38a5) showed continuous, reciprocal expression (Data S4G), consistent with the smooth molecular transitions described for endothelial cells associated with arteries or veins”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“IC 19 represented this difference in a graded rather than categorical way, as Rgs5/Acta2 expression and IC cell scores were continuously, rather than bimodally, distributed across these cells”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Among SMA cells, Acta2 expression correlates with a veinous versus arterial distribution”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“A single IC (IC 13) appeared to encode this distinction, with pericyte marker Vtn as the strongest loading gene”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Like Vanlandewijck et al., we observed (Figure 5) distinct endothelial cell types carrying known arterial (e.g., Bmx; VECA) and venous (Slc38a5; VECV) markers, as well as capillary endothelial cells (VECC) expressing Meox1.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Vanlandewijck et al. described two brain fibroblast-like cell types expressing fibril-forming collagens (e.g., Col1a1, Col1a2), collagen fiber crosslinking proteins (Lum, Dcn), and the platelet-derived growth factor receptor alpha, Pdgfra, which was interposed between astrocyte endfeet and vascular endothelial cells.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“In vivo, αSMA and calponin expression are restricted to mural cells along brain arterioles and arteries [38], however, these markers are often upregulated during culture [39], complicating identification of pericytes.”
From Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D (2019) · cites this paper as [38]
In the citing paper
“APOE in the brain is primarily synthesized by astrocytes and microglia, as indicated by a recent single cell RNA-seq study in the mouse (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Pericytes, SMCs, and endothelial cells express thousands of transcripts encoding different transporters, receptors, active efflux pumps, ion channels, and regulatory molecules (28, 72, 86, 129, 242, 358, 359, 610, 675, 678), whose expression pattern varies by zonation along the arteriocapillary-venous axis and cell type (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“In contrast to the BBB endothelium's gradual phenotypic change along the arteriovenous axis, mural cells formed two distinct groups comprising pericyte and venous SMCs, and arterial and arteriole SMCs (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Briefly, this study is the first to report that at the BBB endothelium transcription factors predominated at arteries and arterioles, transporters predominated capillaries and veins, and ribosomal proteins indicative of protein synthesis were spread along the arteriovenous axis (610), yielding important insights to biological functions and endothelial specialization along the brain vasculature”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“According to a transcriptomic analysis of cells in the vasculature, Plcg2 seems to be expressed in certain subtypes of endothelial cells, although at lower level than compared to microglia (http://betsholtzlab.org/VascularSingleCells/database.html [43]).”
From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [43]
In the citing paper
“we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types [27].”
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 [27]
In the citing paper
“Here, we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types.34”
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 [34]
In the citing paper
“WAVE2 is expressed at high levels in microglia and vascular endothelial cells14,15.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [14]
In the citing paper
“In addition to astrocytes and microglia, other cell types in the brain have been reported to produce ApoE under different conditions. These cells include oligodendrocytes, pericytes, vascular smooth muscle cells, perivascular fibroblasts, and perivascular macrophages [107–109].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [108]
In the citing paper
“PDGFRβ expression in pericytes is noticeably higher than in SMCs18,25,26.”
From Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction (2019) · cites this paper as [25]
In the citing paper
“Based on marker gene enrichment (Table S1), Endo.1 may correspond to endothelial capillary cells, Endo.2 to venous endothelial cells, and Endo.3 to arterial endothelial cells (Vanlandewijck et al., 2018).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“We spatially mapped the developing arterio-venous zonation in the embryonic LV ChP in whole explants by combining the pan-endothelial marker PECAM1 with markers for arteries (Acta2+, Vwf+) and veins (Acta2−, Vwf+) (Vanlandewijck et al., 2018).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Vanlandewijck et al., 2018
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BackgroundVascular Endothelial Protein Tyrosine Phosphatase Regulates Endothelial Function
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“Consistent with previous reports, this suggests that this cluster could be pericytes contaminated with endothelial cell fragments, and thus was not considered for further analysis (He et al., 2016; Vanlandewijck et al., 2018; Yang et al., 2021).”
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“Recent studies suggest that, perhaps because of zonal differences in BBB composition and other properties (as shown in mice and postmortem human brains [211, 212]), the aging brain is especially prone to BBB damage in the hippocampal and wider medial temporal lobe regions.”
BackgroundTransferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA.
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BackgroundInfluentialSevoflurane impairs m6A-mediated mRNA translation and leads to fine motor and cognitive deficits
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“2 (Kcnj12) transcripts in pericytes (Vanlandewijck et al., 2018).”
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“In addition, cell atlases of the vasculatures in the mouse brain and lung were illustrated [27, 28].”
BackgroundThe Active Role of Pericytes During Neuroinflammation in the Adult Brain
Medina‐Flores, F., Hurtado‐Alvarado, G., Deli, M. A., & Gómez‐González, B. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01208-5 · Cited by 63
“Single-cell transcriptomics have shown that capillary pericytes express several members of the connexin (Cx) family, high mRNA expression has been shown for Cx37 and Cx45, and low mRNA expression for Cx26 and Cx43 (He et al. 2018; Vanlandewijck et al. 2018).”
BackgroundInfluentialRemodeling of the Neurovascular Unit Following Cerebral Ischemia and Hemorrhage
Satō, Y., Falcone-Juengert, J., Tominaga, T., Su, H., & Liu, J. (2022) · Cells · doi:10.3390/cells11182823 · Cited by 60
“A recent scRNAseq study suggests that pericytes do have the molecular machinery to regulate vessel diameter since capillary pericytes express receptors for vasoactive mediators including L-type voltage-gated calcium channels and those involved in smooth muscle cell actomyosin contraction [34], providing pivotal suppor…”
BackgroundHow does neurovascular unit dysfunction contribute to multiple sclerosis?
Cashion, J. M., Young, K. M., & Sutherland, B. A. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106028 · Cited by 58
“depending on the vascular zone they occupy.[25] CNS endothelial cells regulate the transport of oxygen and nutrients from the blood into the brain and contribute to waste removal.”
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“ACTA2 + cells in cluster 9 could be further classified as VSMCs based on the high expression of MCAM , MYH11 , TPM1 and TAGLN 24,25 .”
BackgroundMethodBasement Membrane Changes in Ischemic Stroke
Kang, M., & Yao, Y. (2020) · Stroke · doi:10.1161/strokeaha.120.028928 · Cited by 59
“It exists in either a matrix-associated form found at cerebrovascular BM and neuromuscular junction or a transmembrane form expressed mainly by neurons.66–69 In the brain, agrin is produced by neurons, glia, and vascular cells.66,68,70,71 A recent single cell-RNAseq analysis reports that agrin is synthesized by endoth…”
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A single-cell map of antisense oligonucleotide activity in the brain
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Blood-brain barrier models: Rationale for selection
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“These vascular mural cell and astrocyte abnormalities were not observed in S1pr ecTKO retinas (Figures S1F and S1G), suggesting that loss of S1pr1 and S1pr2 in pericytes and astrocytes (Vanlandewijck et al., 2018) contributed these phenotypes in S1pr gTKO retinas.”
BackgroundSelf-citationVascular PDGFR-alpha protects against BBB dysfunction after stroke in mice
Nguyen, Q. L., Okuno, N., Hamashima, T., Dang, S. T., Fujikawa, M., Ishii, Y., Enomoto, A., Maki, T., Nguyen, H. N. A., Nguyen, V. T., et al. (2020) · Angiogenesis · doi:10.1007/s10456-020-09742-w · Cited by 54
“Additionally, platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are abundantly expressed in the central nervous system (CNS) [9] and have recently become attractive therapeutic targets for BBB dysfunction [10, 11].”
BackgroundInfluentialSelf-citationEndothelial cell invasion is controlled by dactylopodia
Figueiredo, A. M., Barbacena, P., Russo, A. M., Vaccaro, S., Ramalho, D., Pena, A., Lima, A. P., Ferreira, R. R., Fidalgo, M., Marjou, F. E., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023829118 · Cited by 51
“ECs express mostly two isoforms of NNMII, NNMIIA and NNMIIB, which are coded by Myh9 and Myh10, respectively (betsholtzlab.org/VascularSingleCells/database.html) (22).”
Ando, K., Тонг, Л., Peng, D., Vázquez-Liébanas, E., Chiyoda, H., He, L., Liu, J., Kawakami, K., Mochizuki, N., Fukuhara, S., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.04.019 · Cited by 53
Self-citationClaudin5 protects the peripheral endothelial barrier in an organ and vessel-type-specific manner
Richards, M., Nwadozi, E., Pal, S., Martinsson, P., Kaakinen, M., Gloger, M., Sjöberg, E., Koltowska, K., Betsholtz, C., Eklund, L., et al. (2022) · eLife · doi:10.7554/elife.78517 · Cited by 55
Self-citationMo, C., Li, H., Yan, M., Xu, S., Wu, J., Li, J., Yang, X., Li, Y., Yang, J., Su, X., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.008 · Cited by 59
Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier
Xie, Y., Yang, F., He, L., Huang, H., Chao, M., Cao, H., Hu, Y., Fan, Z., Zhai, Y., Zhao, W., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.07.026 · Cited by 63
Self-citationEmerging molecular mechanisms of vascular dementia
Romay, M. C., Toro, C., & Iruela‐Arispe, M. L. (2019) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000502 · Cited by 56
DIAPH1 Variants in Non–East Asian Patients With Sporadic Moyamoya Disease
Kundishora, A. J., Peters, S. T., Pinard, A., Durán, D., Panchagnula, S., Barak, T., Miyagishima, D. F., Dong, W., Smith, H. L., Ocken, J., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.1681 · Cited by 55
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Wojtas, A., Dammer, E. B., Guo, Q., Ping, L., Shantaraman, A., Duong, D. M., Yin, L., Fox, E. J., Seifar, F., Lee, E. B., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13821 · Cited by 57
Zhu, Z., Chen, J., Lin, Y., Zhang, C., Li, W., Qiao, H., Fu, M., Dang, E., & Wang, G. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.11.022 · Cited by 52
The Role of Basement Membranes in Cerebral Amyloid Angiopathy
Howe, M. D., McCullough, L. D., & Urayama, A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.601320 · Cited by 50
Schaffenrath, J., Wyss, T., He, L., Rushing, E. J., Delorenzi, M., Vasella, F., Regli, L., Neidert, M. C., & Keller, A. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab022 · Cited by 51
Self-citationHuman Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells: Current Controversies
Lu, T. M., Durán, J. G. B., Houghton, S., Rafii, S., Redmond, D., & Lis, R. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.642812 · Cited by 54
Laminin regulates oligodendrocyte development and myelination
Kang, M., & Yao, Y. (2021) · Glia · doi:10.1002/glia.24117 · Cited by 56
Ah-Pine, F., Khettab, M., Bedoui, Y., Slama, Y., Daniel, M., Doray, B., & Gasque, P. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01605-x · Cited by 66
Pericyte Plasticity in the Brain
Santos, G. S. P., Magno, L. A. V., Romano‐Silva, M. A., Mintz, A., & Birbrair, A. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0296-5 · Cited by 53
van Kuijk, K., Kuppe, C., Betsholtz, C., Vanlandewijck, M., Kramann, R., & Sluimer, J. C. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz185 · Cited by 52
“Thus far, the first groups confirmed the basal atherosclerotic plaque immune cell compositions and have described subtype heterogeneity thereof, and uncovered a potential new macrophage subtype, while SCS of ECs in healthy brain and lung vasculature revealed EC zonation, and arterial- and venous-specific vSMC types.(4…”
BackgroundMethodInfluentialSelf-citationSystematic Identification of Cell-Cell Communication Networks in the Developing Brain
Sheikh, B. N., Bondareva, O., Guhathakurta, S., Tsang, T. H., Sikora, K., Aizarani, N., Sagar, Holz, H., Grün, D., Hein, L., et al. (2019) · iScience · doi:10.1016/j.isci.2019.10.026 · Cited by 53
“273 studies have utilized transgenic approaches such as Tie2-GFP (Daneman et al., 2010a; Zhang et al., 2014) and Cldn5-GFP (Vanlandewijck et al., 2018) animals for the isolation of endothelial cells.”
BackgroundMethodInfluentialVesicular Transport Machinery in Brain Endothelial Cells: What We Know and What We Do not
Tóth, A. E., Holst, M. R., & Nielsen, M. S. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200212113421 · Cited by 56
Li, Z., Korhonen, E. A., Merlini, A., Strauss, J., Wihuri, E., Nurmi, H., Antila, S., Paech, J., Deutsch, U., Engelhardt, B., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci130308 · Cited by 52
“CD45 + immune cells and CD31 + ECs were enriched from the SCs by using the Neural Tissue Dissociation Kit (P) and Myelin Removal Beads II (Miltenyi Biotec) as described previously (27).”
MethodSLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function
Bae, M. H., Roh, J. D., Kim, Y.-J., Kim, S. S., Han, H. M., Yang, E., Kang, H., Lee, S., Kim, J. Y., Kang, R., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202012632 · Cited by 54
“4 of 27 EMBO Molecular Medicine 13: e12632 | 2021 ª 2021 The Authors et al, 2016; Vanlandewijck et al, 2018).”
BackgroundA human brain vascular atlas reveals diverse cell mediators of Alzheimer’s disease risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Maat, C. A., Losada, P. M., Chen, M. B., Agam, M., Schaum, N., Khoury, N., et al. (2021) · doi:10.1101/2021.04.26.441262 · Cited by 48
Self-citationPericyte‐secreted IGF2 promotes breast cancer brain metastasis formation
Molnár, K., Mészáros, Á., Fazakas, C., Kozma, M., Győri, F., Reisz, Z., Tiszlavicz, L., Farkas, A. E., Nyúl‐Tóth, Á., Haskó, J., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12752 · Cited by 53
Breaching the Blood–Brain Tumor Barrier for Tumor Therapy
Marcucci, F., Corti, A., & Ferreri, A. J. M. (2021) · Cancers · doi:10.3390/cancers13102391 · Cited by 51
“Likewise, astrocytes, pericytes, microglia cells and neurons exhibit important specializations, and recent investigations on single-cell components of the NVU have confirmed the organotypic molecular signatures of these cells [5,6].”
BackgroundRungta, R. L., Zuend, M., Aydin, A.-K., Martineau, É., Boido, D., Weber, B., & Charpak, S. (2021) · Communications Biology · doi:10.1038/s42003-021-02382-w · Cited by 53
Dach1 Extends Artery Networks and Protects Against Cardiac Injury
Raftrey, B. C., Williams, I. M., Coronado, P. E. R., Fan, X., Chang, A. H., Zhao, M., Roth, R., Trimm, E., Racelis, R., D’Amato, G., et al. (2021) · Circulation Research · doi:10.1161/circresaha.120.318271 · Cited by 45
“This is consistent with previous analyses showing that brain and heart capillary ECs exist along a continuum of arterial-venous identity, even in adults (Chen et al., 2020; Su et al., 2018; Vanlandewijck et al., 2018).”
ResultNeurovascular adaptations modulating cognition, mood, and stress responses
Dion‐Albert, L., Dudek, K., Russo, S. J., Campbell, M., & Ménard, C. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.01.005 · Cited by 58
Stroke-induced damage on the blood–brain barrier
Xue, S., Zhou, X., Yang, Z., Si, X., & Sun, X. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1248970 · Cited by 58
“Strong evidence for the role of pericytes in controlling vessel diameter is provided by the presence of receptors for vasoactive factors, such as L-type voltage-gated calcium channels, and those involved in the contraction of smooth muscle cell actin on pericytes (76).”
Dudek, K., Paton, S. E. J., Binder, L. B., Collignon, A., Dion‐Albert, L., Cadoret, A., Lebel, M., Lavoie, O., Bouchard, J., Kaufmann, F. N., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01891-9 · Cited by 59
“…Cldn5 -deficient mice die within 10 h of birth 28 , and it allows downregulation of Cldn5 in a region-and cell-specific manner, with this tight junction being expressed only in endothelial cells 29 , leading to functional deficits with leakage of circulating dyes or proteins into the brain 3,30 .”
Trost, A., Bruckner, D., Rivera, F. J., & Reitsamer, H. A. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-11093-2_1 · Cited by 55
Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications
Nwadozi, E., Rudnicki, M., & Haas, T. L. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00077 · Cited by 53
“This idea is supported by recent single cell profiling of brain and lung derived pericytes1 (He et al., 2018; Vanlandewijck et al., 2018) that revealed a non-overlapping expression profile of 1http://betsholtzlab.org/VascularSingleCells/database.html lineage specific regulators including Runx2…”
BackgroundCerebral cavernous malformations are driven by ADAMTS5 proteolysis of versican
Hong, C. C., Tang, A. T., Detter, M. R., Choi, J. P., Wang, R., Yang, X., Guerrero, A. A., Wittig, C. F., Hobson, N., Girard, R., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200140 · Cited by 51
Fibroblasts repair blood-brain barrier damage and hemorrhagic brain injury via TIMP2
Xu, L., Nirwane, A. M., Xu, T., Kang, M., Devasani, K., & Yao, Y. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111709 · Cited by 53
Zhang, K., Chen, F., Wang, L., & Hu, J. (2023) · Small · doi:10.1002/smll.202206044 · Cited by 52
Korte, N., James, G., You, H., Hirunpattarasilp, C., Christie, I., Sethi, H., & Attwell, D. (2023) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x231152549 · Cited by 49
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
Li, Z., Antila, S., Nurmi, H. J., Chilov, D., Korhonen, E. A., Fang, S., Karaman, S., Engelhardt, B., & Alitalo, K. K. (2023) · Science Immunology · doi:10.1126/sciimmunol.abq0375 · Cited by 51
Holl, D., Hau, W. F., Julien, A., Banitalebi, S., Kalkitsas, J., Savant, S., Llorens-Bobadilla, E., Hérault, Y., Pavlovic, G., Amiry-Moghaddam, M. R., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01678-4 · Cited by 52
“To specifically target Col1a1 -expressing fibroblasts in the adult CNS, we used an inducible Col1a1-CreER T2 mouse line (Methods) and crossed it to the R26R-tdTomato reporter mouse line.”
InfluentialDynamic fibroblast–immune interactions shape recovery after brain injury
Ewing-Crystal, N. A., Mroz, N. M., Larpthaveesarp, A., Lizama, C. O., Pennington, R., Chiaranunt, P., Dennis, J. I., Chang, A. A., Merrill, E. D., Caryotakis, S. E., et al. (2025) · Nature · doi:10.1038/s41586-025-09449-2 · Cited by 65
Zhou, H. J., Qin, L., Jiang, Q., Murray, K. N., Zhang, H., Li, B., Lin, Q., Graham, M. M., Liu, X., Grutzendler, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20774-0 · Cited by 55
Pericytes Across the Lifetime in the Central Nervous System
Bennett, H. C., & Kim, Y. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.627291 · Cited by 49
Bioprinted microvasculature: progressing from structure to function
Seymour, A. J., Westerfield, A. D., Cornelius, V., Skylar‐Scott, M. A., & Heilshorn, S. C. (2022) · Biofabrication · doi:10.1088/1758-5090/ac4fb5 · Cited by 56
“…of the need for models that elucidate neurological diseases, and the importance of brain vasculature and the BBB to neurological health and treatment of disease, there has been growing interest in finely characterizing markers for and the localization of vascular cells in the brain [188, 189].”
A phase 2 study of thalidomide for the treatment of radiation-induced blood-brain barrier injury
Cheng, J., Jiang, J., He, B., Lin, W., Li, Y., Duan, J., Li, H., Huang, X., Cai, J., Xie, J., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abm6543 · Cited by 54
Ye, Q., Jo, J.-Y., Wang, C., Oh, H., Zhan, J., Choy, T. J., Kim, K. I., D’Alessandro, A., Reshetnyak, Y. K., Jung, S. Y., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114193 · Cited by 54
“While our study found very low expression of CCR2 mRNA and protein in normal or stroked WT brain, consistent with previous endothelial transcriptome atlases, 70,71 we found that loss of Slc4a4 results in an upregulation of endothelial CCR2, contributing to exacerbated BBB damage after stroke.”
Czupalla, C. J., Yousef, H., Wyss‐Coray, T., & Butcher, E. C. (2018) · BIO-PROTOCOL · doi:10.21769/bioprotoc.3092 · Cited by 48
“In the last decade, several protocols for brain endothelial isolation have been employed predominantly in BBB developmental studies (Daneman et al., 2010; Vanlandewijck et al., 2018).”
Engelbrecht, E., Levesque, M. V., He, L., Vanlandewijck, M., Nitzsche, A., Niazi, H., Kuo, A., Singh, S. A., Aikawa, M., Holton, K. M., et al. (2020) · eLife · doi:10.7554/elife.52690 · Cited by 52
“Library preparation from single cells was performed as previously described (Vanlandewijck et al., 2018).”
MethodSelf-citationUnderstanding angiodiversity: insights from single cell biology
Jakab, M., & Augustin, H. G. (2020) · Development · doi:10.1242/dev.146621 · Cited by 51
Yahn, S. L., Li, J., Goo, I., Gao, H., Brambilla, R., & Lee, J. K. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104674 · Cited by 45
Metadata
- Authors
- Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., Sun, Y., Raschperger, E., Räsänen, M., Zarb, Y., Mochizuki, N., Keller, A., Lendahl, U., & Betsholtz, C.
- Affiliations
- Uppsala University (SE)
- Tianjin Medical University General Hospital (CN)
- Karolinska Institutet (SE)
- University of Zurich (CH)
- Japan Agency for Medical Research and Development (JP)
- Corresponding author
- Betsholtz, Christer
- ORCID
- Venue
- Nature
- Published
- 2018-02-14
- Volume
- 554
- Issue
- 7693
- Pages
- 475-480
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2786318872
- Semantic Scholar
- 237e37a314d2faef1d389b147614e8fa550a3087
- Cited by
- 1,892
- References
- 65
- Citations by year
- 2026: 197 · 2025: 244 · 2024: 275 · 2023: 234 · 2022: 258 · 2021: 271 · 2020: 222 · 2019: 125 · 2018: 65
- FWCI
- 74.80
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-06-20)
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (159514)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Keywords
- cerebral vasculature, blood-brain barrier, endothelial cells, mural cells, pericytes, smooth muscle cells, perivascular cells, single-cell transcriptomics, cerebrovascular disease, mouse brain
- MeSH terms
- Animals, Arteries, Arterioles, Blood Vessels, Brain, Capillaries, Female, Fibroblasts, Male, Organ Specificity, Veins, Pericytes, Myocytes, Smooth Muscle, Endothelial Cells, Mice, Single-Cell Analysis, Transcriptome
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