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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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“While robust ATP1A2 signals were associated with most PDGFRBþ nuclei, we observed a comparative lack of ATP1A2 signal in PDGFRBþ nuclei in a large diameter vessel (Supplementary Figure S9), consistent with enriched expression in pericytes compared to VSMCs.”
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“Transcriptomics study with single cell RNA sequencing has shown a seamless continuum of transcriptional states of endothelial cells as they transition from arterial into capillary and then venous phenotypes (zonation), with the prevalence of BBBassociated trans-endothelial molecular transporters in capillaries and vei…”
BackgroundContractile apparatus in CNS capillary pericytes
Erdener, Ş. E., Küreli, G., & Dalkara, T. (2022) · Neurophotonics · doi:10.1117/1.nph.9.2.021904 · Cited by 30
“brain vasculature, which found a large amount of α-SMA mRNA in vSMCs, whereas low hits were detected in pericytes.(30,44)”
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“Recent transcriptomic studies, such as Vanlandewijck et al. (2018) suggest that these cells may represent vascular fibroblast-like cells rather than pericytes (personal communication) especially after long term culture.”
BackgroundPericyte Progenitor Coupling to the Emerging Endothelium During Vasculogenesis via Connexin 43
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BackgroundMethodMutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
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“…RNA sequencing (scRNA-seq) studies have begun to systematically catalog cell types of the developing and mature human cerebrovasculature, expanding knowledge about perivascular cell diversity and de fi ning endothelial cell molecular signatures correlated with arteriovenous segmentation 46,47 .”
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“Single cell transcriptomic studies (23) and physiological studies both in vivo (24) and in vitro (25) also confirm that capillary pericytes express high levels of receptors for vasoconstrictive signaling, such as endothelin-1 type A receptors and thromboxane A2 receptors, potentially involved in basal capillary tone r…”
BackgroundThe influence of physiological and pathological perturbations on blood-brain barrier function
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“Recent transcriptomic atlases for mouse and human brain have highlighted differences in gene expression of cells in the NVU along the arterio-venous axis (Vanlandewijck et al., 2018; Garcia et al., 2022; Jeong et al., 2022; Yang A. C. et al., 2022; Crouch et al., 2023; Sun et al., 2023).”
BackgroundAdenosine and adenosine receptors in metabolic imbalance-related neurological issues
Jang, M., & Song, J. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116996 · Cited by 30
Interaction of microglia with the microenvironment in spinal cord injury
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Dobryakova, Y. V., Volobueva, M. N., Манолова, А. О., Medvedeva, T. M., Kvichansky, A. A., Gulyaeva, N. V., Markevich, V. A., Stepanichev, M. Y., & Bolshakov, A. P. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00146 · Cited by 26
“(Zeisel et al., 2015, 2018; Vanlandewijck et al., 2018), and are associated with transport functions of these cells or regulation of this function.”
BackgroundWeber, G. M., Ju, Y., & Börner, K. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00029 · Cited by 26
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Faulhaber, L. D., Phuong, A. Q., Hartsuyker, K. J., Cho, Y., Mand, K. K., Harper, S. D., Olson, A. K., Garden, G. A., Shih, A. Y., & Gust, J. (2021) · Brain Communications · doi:10.1093/braincomms/fcab309 · Cited by 31
“Additionally, single-cell gene expression analysis of the mouse neurovascular unit shows low to undetectable CD19 expression in pericytes or vascular smooth muscle cells.(64,74) We did observe gaps in the coverage of pericyte processes in mice with severe behavioural neurotoxicity, the mechanism and consequences of wh…”
BackgroundOue, H., Yamazaki, Y., Qiao, W., Yuanxin, C., Ren, Y., Kurti, A., Shue, F., Parsons, T. M., Perkerson, R. B., Kawatani, K., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.163822 · Cited by 26
“cular-related cell types (pericyte/venous SMC, arterial SMC/arteriole SMC, and fibroblast-like cells) (26).”
Liu, R., Collier, J. M., Abdul‐Rahman, N., Capuk, O., Zhang, Z., & Begum, G. (2024) · Aging and Disease · doi:10.14336/ad.2023.1201 · Cited by 31
“Capillary pericytes express the Ca 2+ activated Cl - channel, TMEM16A or anoctamin and several members of voltage dependent ClC family: ClC-2, -3, -4, -6 and -7 [30].”
BackgroundAlterations of the blood-brain barrier during aging
Cao, Y., Xu, W., & Liu, Q. (2024) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x241240843 · Cited by 30
“87,103,104 In a healthy brain, some studies consider CNS fibroblasts to be part of the support of the BBB structure, while others suggest that CNS fibroblasts are involved in the glymphatic system.”
BackgroundPapain-based Single Cell Isolation of Primary Murine Brain Endothelial Cells Using Flow Cytometry
Yousef, H., Czupalla, C. J., Lee, D. P., Butcher, E. C., & Wyss‐Coray, T. (2018) · BIO-PROTOCOL · doi:10.21769/bioprotoc.3091 · Cited by 26
“In the last decade, several protocols for brain endothelial cell isolation have been employed, which tend to use transgenic endothelial cells labeled with fluorescent proteins such as GFP (Daneman et al., 2010; Vanlandewijck et al., 2018).”
Immune surveillance of brain metastatic cancer cells is mediated by IFITM1
She, X., Shen, S., Chen, G., Gao, Y., Ma, J., Gao, Y., Liu, Y., Gao, G., Zhao, Y. F., Wang, C., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022111112 · Cited by 24
“Single-cell RNA sequencing of healthy mouse brain tissue showed very little to no expression of C3aR1 in cell types other than microglia (Zhang et al, 2014; He et al, 2018; Vanlandewijck et al, 2018; Harder et al, 2020).”
BackgroundRegulation of YAP Promotor Accessibility in Endothelial Mechanotransduction
Mannion, A. J., Zhao, H., Zhang, Y., von Wright, Y., Bergman, O., Roy, J., Saharinen, P., & Holmgren, L. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.320300 · Cited by 26
Chasseigneaux, S., Cochois, V., Lecorgne, L., Lochus, M., Nicolic, S., Blugeon, C., Jourdren, L., Gomez‐Zepeda, D., Tenzer, S., Sanquer, S., et al. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00526-8 · Cited by 27
“As previously reported [31, 48, 49, 53], we confirm here that Pparg transcripts are barely detectable in brain endothelial cells and that PPAR target genes are not induced by rosiglitazone at pharmaco-logically active concentration (1 µM).”
InfluentialEndothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction
Hansen, C. E., Vacondio, D., van der Molen, L., Jüttner, A. A., Fung, W. K., Karsten, M., van het Hof, B., Fontijn, R. D., Kooij, G., Witte, M. E., et al. (2025) · Cell Death & Disease · doi:10.1038/s41419-024-07306-0 · Cited by 27
“Furthermore, the WM of the EC-KO animals demonstrates IgG leakage and increased glial cell reactivity near the vasculature, which coincided with immune cell in fi ltration in the brain parenchyma.”
Cancer brain metastasis: molecular mechanisms and therapeutic strategies
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“As BMs formed in the brain, the BBB is disrupted and replaced by BTB [137].”
Vrillon, A., Ashton, N. J., Bouaziz-Amar, É., Mouton‐Liger, F., Cognat, E., Dumurgier, J., Lilamand, M., Karikari, T. K., Prévot, V., Zetterberg, H., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105694 · Cited by 29
Creating Lineage Trajectory Maps Via Integration of Single‐Cell RNA‐Sequencing and Lineage Tracing
Fletcher, R. B., Das, D., & Ngai, J. (2018) · BioEssays · doi:10.1002/bies.201800056 · Cited by 25
Tight junction modulators for drug delivery to the central nervous system
Hashimoto, Y., Tachibana, K., & Kondoh, M. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.05.007 · Cited by 25
Advancing brain barriers RNA sequencing: guidelines from experimental design to publication
Francisco, D. M. F., Marchetti, L., Rodríguez‐Lorenzo, S., Frías-Anaya, E., de Figueiredo, R. M., BtRAIN Network, Heymans, M., Culot, M., Santa-Maria, A. R., Deli, M. A., et al. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00207-2 · Cited by 24
“For example, FACS has been successfully used to enrich brain endothelial cells isolated from claudin-5-GFP mice [13] or tamoxifen-treated Rosa-tdTomato; VE-Cadherin-CreERT2 mice [14].”
BackgroundMethodResultInfluentialVascular underpinning of COVID-19
Wazny, V. K., Siau, A., Wu, K. X., & Cheung, C. (2020) · Open Biology · doi:10.1098/rsob.200208 · Cited by 24
Grochowska, M. M., Mascaro, A. C., Boumeester, V., Natale, D., Breedveld, G. J., Geut, H., van Cappellen, W. A., Boon, A. J. W., Kievit, A. J. A., Sammler, E. M., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02313-3 · Cited by 22
Warmke, N., Platt, F. M., Bruns, A. F., et al. (2021) · Endocrinology · doi:10.1210/endocr/bqab182 · Cited by 25
Edgerton-Fulton, M., & Ergul, A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00072.2022 · Cited by 29
Murrant, C. L., & Fletcher, N. M. (2022) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00088.2022 · Cited by 29
He, H., Wu, Y., Su, N., Zhang, C., Dai, J., Han, F., Singhal, M., Bai, W., Zhu, X., Zhu, J., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211422 · Cited by 25
“Further analysis of previously published single-cell RNA expression data (Vanlandewijck et al., 2018) confirmed the differential expression levels of sGC in pericytes and vSMCs (Fig.”
BackgroundLessons of Vascular Specialization From Secondary Lymphoid Organ Lymphatic Endothelial Cells
Arroz‐Madeira, S., Bekkhus, T., Ulvmar, M. H., & Petrova, T. V. (2023) · Circulation Research · doi:10.1161/circresaha.123.322136 · Cited by 27
Shima, Y., Sasagawa, S., Ota, N., Oyama, R., Tanaka, M., Kubota‐Sakashita, M., Kawakami, H., Kobayashi, M., Takubo, N., Ozeki, A. N., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abq7721 · Cited by 26
The Transcriptional Landscape of Pericytes in Acute Ischemic Stroke
Buizza, C., Enström, A., Carlsson, R., & Paul, G. (2023) · Translational Stroke Research · doi:10.1007/s12975-023-01169-x · Cited by 26
Song, W., Beigneux, A. P., Weston, T. A., Chen, K., Yang, Y., Nguyen, L. P., Guagliardo, P. R., Jung, H., Tran, A. P., Tu, Y., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2313825120 · Cited by 25
“GPIHBP1 expression is also absent in brain capillaries (55).”
An integral blood–brain barrier in adulthood relies on microglia-derived PDGFB
Weng, Y., Chen, N., Zhang, R., He, J., Ding, X., Cheng, G., Bi, Q., Lu, Y., Shen, X. Z., Wan, S., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.11.023 · Cited by 25
Phillips, B., Clark, J., Martineau, É., & Rungta, R. L. (2023) · Communications Biology · doi:10.1038/s42003-023-04858-3 · Cited by 26
Zamboulis, D. E., Marr, N., Lenzi, L., Birch, H. L., Screen, H. R. C., Clegg, P., & Thorpe, C. T. (2023) · Aging and Disease · doi:10.14336/ad.2023.0425-1 · Cited by 26
Isaacs, D. P., Xiang, L., Hariharan, A., & Longden, T. A. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2405965121 · Cited by 29
“Based on thin - strand pericyte ion channel gene expression profile from a public dataset ( 29 ) and our prior studies implicating thin - strand pericyte K ATP channels as energy substrate sensors in the brain ( 20 ), we chose to study the role of these channels during NVC.”
Ion channels in capillary endothelium
Garcia, D. C. G., & Longden, T. A. (2020) · Current topics in membranes · doi:10.1016/bs.ctm.2020.01.005 · Cited by 23
Lack of Flvcr2 impairs brain angiogenesis without affecting the blood-brain barrier
Santander, N. G., Lizama, C. O., Meky, E. M., McKinsey, G. L., Jung, B., Sheppard, D., Betsholtz, C., & Arnold, T. D. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136578 · Cited by 26
“…expression is also detected in pericytes in a single-cell transcriptomic data set, albeit at lower level and/or in a smaller subset of the cells (16), it is possible that some of the GFP signal emanates from pericytes; however, this would be hard to unequivocally establish, given the stronger…”
Self-citationCarrier, M., Guilbert, J., Lévesque, J.-P., Tremblay, M., & Desjardins, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.595002 · Cited by 23
Blood–Brain Barrier Mechanisms in Stroke and Trauma
Li, W., Cao, F., Takase, H., Arai, K., Lo, E. H., & Lok, J. M. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_426 · Cited by 26
New Tricks for an Old (Hedge)Hog: Sonic Hedgehog Regulation of Astrocyte Function
Garcia, A. D. R. (2021) · Cells · doi:10.3390/cells10061353 · Cited by 25
The Interplay Between Brain Vascular Calcification and Microglia
Maheshwari, U., Huang, S., Sridhar, S., & Keller, A. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.848495 · Cited by 24
Self-citationPerivascular Mesenchymal Stem/Stromal Cells, an Immune Privileged Niche for Viruses?
Lebeau, G., Ah-Pine, F., Daniel, M., Bedoui, Y., Vagner, D., Frumence, É., & Gasque, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23148038 · Cited by 25
“RNA profiling of mouse brain vasculature revealed a rather unique pool of perivascular cells made of a two pericyte clusters and three subsets of perivascular fibroblasts [69,75].”
BackgroundLugano, R., Vemuri, K., Barbera, S., Orlandini, M., Dejana, E., Claesson, L., & Dimberg, A. (2023) · The FASEB Journal · doi:10.1096/fj.202201623rr · Cited by 25
“28 The contribution of endothelial barrier dysfunction to several disorders including psychiatric and 29 suggests a possible protective role for vascular CD93 in the development of neurological conditions.”
BackgroundGoldwaser, E. L., Wang, D. J. J., Adhikari, B. M., Chiappelli, J., Shao, X., Yu, J., Lu, T., Chen, S., Marshall, W., Yuen, A., et al. (2023) · Schizophrenia Bulletin · doi:10.1093/schbul/sbad057 · Cited by 23
Parab, S., Card, O. A., Chen, Q., America, M., Buck, L. D., Quick, R. E., Horrigan, W. F., Levkowitz, G., Vanhollebeke, B., & Matsuoka, R. L. (2023) · eLife · doi:10.7554/elife.86066 · Cited by 27
“, 2020) and even within the same tissue (Kalucka et al., 2020; Matsuoka et al., 2022; Vanlandewijck et al., 2018).”
BackgroundMironova, G. Y., Kowalewska, P. M., El‐Lakany, M. A., Tran, C. H. T., Sancho, M., Zechariah, A., Jackson, W. F., & Welsh, D. G. (2023) · Physiological Reviews · doi:10.1152/physrev.00035.2022 · Cited by 27
Jones, H. E., Coelho‐Santos, V., Bonney, S. K., Abrams, K. A., Shih, A. Y., & Siegenthaler, J. A. (2023) · Development · doi:10.1242/dev.201805 · Cited by 35
“…within the neurovascular unit, PVFs are uniquely positioned to provide support to vascular structures and cell types, potentially via secretion or modification of extracellular matrix proteins such as type I and III collagens (Hannocks et al., 2018; Vanlandewijck et al., 2018; Yang et al., 2022).”
BackgroundInfluentialSakuma, R., Takahashi, A., Nakano‐Doi, A., Sawada, R., Kamachi, S., Beppu, M., Takagi, T., Yoshimura, S., Matsuyama, T., & Nakagomi, T. (2018) · Stem Cells and Development · doi:10.1089/scd.2018.0075 · Cited by 24
“Although iSCs are likely brain PC derivatives, increasing evidence indicates that various types of cells, such as peri-vascular fibroblasts [74–76], oligodendrocyte precursor cells [77,78], and radial glia-like cells [79], also reside near the brain blood vessels.”
Axon Guidance-Related Factor FLRT3 Regulates VEGF-Signaling and Endothelial Cell Function
Jauhiainen, S., Laakkonen, J. P., Ketola, K., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00224 · Cited by 24
“…receptors UNC5A-D, fibroblast growth factor receptors (FGFRs), ROBO1, latrophilin as well as FLRT-FLRT interactions between adjacent cells (Böttcher et al., 2004; Haines et al., 2006; Hampel et al., 2011; Wei et al., 2011; Leyva-Díaz et al., 2014; Seiradake et al., 2014; Jackson et al., 2015).”
Morrison, V. E., Smith, V. N., & Huang, J. K. (2019) · eNeuro · doi:10.1523/eneuro.0270-19.2019 · Cited by 27
“This is consistent with our interrogation of the data in the online gene expression database generated by Vanlandewijck et al. (2018), leading to the conclusion that only a subset of Pdgfr perivascular cells (i.e., FB cells) express Raldh2.”
BackgroundMethodResultInfluentialMesenchymal stromal cells as conductors of adipose tissue remodelingPreprint
Cannavino, J., & Gupta, R. K. (2023) · Genes & Development · doi:10.1101/gad.351069.123 · Cited by 25
CXCL12 defines lung endothelial heterogeneity and promotes distal vascular growth
Chandrasekaran, P., Negretti, N. M., Sivakumar, A., Liberti, D. C., Wen, H., de Nieuwburgh, M. P., Wang, J. Y., Michki, S. N., Chaudhry, F. N., Kaur, S., et al. (2022) · Development · doi:10.1242/dev.200909 · Cited by 26
Microfluidic models of the neurovascular unit: a translational view
Wevers, N. R., & de Vries, H. E. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00490-9 · Cited by 25
“The vessels that make up the NVU come in different diameters, which show differences in their relative permeability, transporter expression, and interaction with perivascular cells [171–173].”
BackgroundSingle-Cell mRNA Sequencing of the Mouse Brain Vasculature
Vanlandewijck, M., & Betsholtz, C. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8712-2_21 · Cited by 21
Self-citationExercise-mediated angiogenesis
Kissane, R. W. P., & Egginton, S. (2019) · Current Opinion in Physiology · doi:10.1016/j.cophys.2019.06.005 · Cited by 22
Deficiency of MFSD7c results in microcephaly-associated vasculopathy in Fowler syndrome
Kalailingam, P., Wang, K. Q., Toh, X. R., Nguyen, Q. T., Chandrakanthan, M., Hasan, Z., Habib, C., Schif, A., Radio, F. C., Dallapiccola, B., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136727 · Cited by 23
Wang, H., Xu, Z., Xia, Z., Rallo, M. S., Duffy, A., & Matise, M. P. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017779118 · Cited by 23
Adenosine A2A Receptor Activation Enhances Blood–Tumor Barrier Permeability in a Rodent Glioma Model
Vézina, A., Manglani, M., Morris, D., Foster, B., McCord, M., Song, H., Zhang, M., Davis, D., Zhang, W., Bills, J., et al. (2021) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0995 · Cited by 24
Wang, Y., Luo, W., Huang, L., Xiao, J., Song, X., Li, F., Ma, Y., Wang, X., Jin, F., Liu, P., et al. (2021) · Theranostics · doi:10.7150/thno.64880 · Cited by 25
Emerging Concepts of Vascular Cell Clonal Expansion in Atherosclerosis
Misra, A., Rehan, R., Lin, A., Patel, S., & Fisher, E. A. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316093 · Cited by 23
Wu, H., Wei, M., Li, Y., Ma, Q., & Zhang, H. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.910543 · Cited by 26
Adnani, L., Spinelli, C., Tawil, N., & Rak, J. W. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.11.003 · Cited by 25
Mäe, M. A., Tian, L., Bertuzzi, G., Raschperger, E., Vanlandewijck, M., He, L., Nahar, K., Dalheim, A. V., Hofmann, J. J., Laviña, B., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35576-0 · Cited by 23
Self-citationOverlapping Protein Accumulation Profiles of CADASIL and CAA
Young, K. Z., Xu, G., Keep, S. G., Borjigin, J., & Wang, M. M. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.11.015 · Cited by 24
Mural Cells: Potential Therapeutic Targets to Bridge Cardiovascular Disease and Neurodegeneration
Lin, A., Peiris, N. J., Dhaliwal, H., Hakim, M., Li, W., Ganesh, S., Ramaswamy, Y., Patel, S., & Misra, A. (2021) · Cells · doi:10.3390/cells10030593 · Cited by 24
Goncalves, A., & Antonetti, D. A. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00386-0 · Cited by 22
“Additionally, using a claudin-12 reporter mouse it was shown that this claudin has a very low expression in BBB ECs, being predominantly expressed in neurons, astrocytes and smooth muscle cells [22, 29].”
BackgroundMethodArbaizar‐Rovirosa, M., Gallizioli, M., Lozano, J. J., Sidorova, J., Pedragosa, J., Figuerola, S., Chaparro‐Cabanillas, N., Boya, P., Graupera, M., Claret, M., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02888-6 · Cited by 23
“Recent single-cell transcriptomics provided relevant information regarding vessel heterogeneity and arterio-venous zonation in the brain [5].”
BackgroundMethodThe contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury
Mokbel, A. Y., Burns, M. P., & Main, B. S. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03122-7 · Cited by 25
Guo, Y., Li, J., Zhang, H., Zi, H., Liu, M., An, Q., Qiu, T., Li, P., Song, J., Liu, P., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae186 · Cited by 27
Dietary salt, vascular dysfunction, and cognitive impairment
Faraco, G. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae229 · Cited by 26
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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