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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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“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
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003748 · Cited by 5,824
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572
Sleep Drives Metabolite Clearance from the Adult Brain
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., et al. (2013) · Science · doi:10.1126/science.1241224 · Cited by 5,411
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
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Cited by
Sorted by citations
Items 801–900 of 1,911
Transient Receptor Potential Channels in Vascular Mechanotransduction
Solano, A. S., Lavanderos, B. J., Metwally, E., & Earley, S. (2024) · American Journal of Hypertension · doi:10.1093/ajh/hpae134 · Cited by 24
Central nervous system vascularization in human embryos and neural organoids
Boutom, S., Silva, T. P., Palecek, S. P., Shusta, E. V., Fernandes, T. G., & Ashton, R. S. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115068 · Cited by 26
Transcriptional profile of the rat cardiovascular system at single-cell resolution
Arduini, A., Fleming, S. J., Xiao, L., Hall, A. W., Akkad, A.-D., Chaffin, M. D., Bendinelli, K. J., Tucker, N. R., Papangeli, I., Mantineo, H., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115091 · Cited by 24
Hinca, S. B., Salcedo, C., Wagner, A., Goldeman, C., Sadat, E., Aibar, M. M. D., Maechler, P., Brodin, B., Aldana, B. I., & Helms, H. C. C. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15207 · Cited by 22
“Aspartate aminotransferases are relatively low expressed in brain endothelial cells relative to GDH (He et al., 2018; Vanlandewijck et al., 2018; Zhang et al., 2014; Zhang, et al., 2016), although the expression level based on transcriptomics may not necessarily translate into actual capacity for…”
BackgroundZebrafish Vascular Mural Cell Biology: Recent Advances, Development, and Functions
Ando, K., Ishii, T., & Fukuhara, S. (2021) · Life · doi:10.3390/life11101041 · Cited by 22
“Brain pericytes are selectively labeled with the abcc9 reporter [2].”
BackgroundInfluentialSelf-citationWalter, F. R., Harazin, A., Tóth, A. E., Veszelka, S., Santa-Maria, A. R., Barna, L., Kincses, A., Biczó, G., Balla, Z., Kui, B., et al. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00308-0 · Cited by 25
Platelet-derived growth factor signalling in neurovascular function and disease
Li, S. Y., Johnson, R. H., Smyth, L. C. D., & Dragunow, M. (2022) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2022.106187 · Cited by 22
De, A., Morales, J. E., Chen, Z., Sebastian, S., & McCarty, J. H. (2022) · Development · doi:10.1242/dev.200472 · Cited by 21
Chan-Andersen, P. C., Romanova, E. V., Rubakhin, S. S., & Sweedler, J. V. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102254 · Cited by 22
The emergence of the calvarial hematopoietic niche in health and disease
Mills, W. A., Coburn, M., & Eyo, U. B. (2022) · Immunological Reviews · doi:10.1111/imr.13120 · Cited by 23
The vasculature of neurogenic niches: Properties and function
Karakatsani, A., Álvarez-Vergara, M. I., & de Almodóvar, C. R. (2023) · Cells and Development · doi:10.1016/j.cdev.2023.203841 · Cited by 25
Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain
Beppu, M., Nakagomi, T., Takagi, T., Nakano‐Doi, A., Sakuma, R., Kuramoto, Y., Tatebayashi, K., Matsuyama, T., & Yoshimura, S. (2019) · Stem Cells and Development · doi:10.1089/scd.2018.0232 · Cited by 22
André, S., Larbanoix, L., Verteneuil, S., Stanicki, D., Nonclercq, D., Elst, L. V., Laurent, S., Müller, R. N., & Burtéa, C. (2020) · Biology · doi:10.3390/biology9070161 · Cited by 25
Endothelial and mural laminin-α5 contributes to neurovascular integrity maintenance
Nirwane, A. M., Kang, M., Aravinthan, A., Maharaj, V., Nguyen, F., Aguilar, E. S., Nasrolahi, A., & Yao, Y. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00521-z · Cited by 23
“In addition to mural cells, PDGFRβ-Cre also labels fibroblasts in the CNS [56–58].”
BackgroundMa, J., Zhang, L., Zhang, X., Zhang, L., Zhang, H., Zhu, Y., Huang, X., Zhang, T., Tang, X., Wang, Y., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.ado5266 · Cited by 22
“Moreover, expanding ECs need to undergo multiple steps to line new lumen to prevent inflammatory cell extravasation and maintain blood perfusion ( 23 – 28 ).”
BackgroundPlog, B. A., Kim, K., Verhaege, D., Kim, M. W., Papadopoulos, Z., Dikranian, K. T., Dykstra, T., Cao, J., Perrin, R. J., Schwetye, K. E., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01977-4 · Cited by 22
“Blood supply to the brain comes from the carotid and vertebral arteries, whereas the blood is drained through postcapillary venules into venules, veins and finally the dural sinuses 17,18 .”
Tian, M., Kawaguchi, R., Shen, Y., Machnicki, M., Villegas, N. G., Cooper, D. R., Montgomery, N., Cai, Y., Haring, J., Lan, R., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.002 · Cited by 24
Whitelaw, B. S., Matei, E. K., & Majewska, A. K. (2020) · eNeuro · doi:10.1523/eneuro.0311-20.2020 · Cited by 20
“Understanding the mechanisms underlying P2Y12 signaling in microglia can provide insight into how extracellular nucleotides are used in the CNS to facilitate communication and interactions between diverse cell types.”
BackgroundInfluentialThe effect of absent blood flow on the zebrafish cerebral and trunk vasculature
Kugler, E., Snodgrass, R. O., Bowley, G., Plant, K., Serbanovic‐Canic, J., Hamilton, N., Evans, P. C., Chico, T., & Armitage, P. A. (2021) · Vascular Biology · doi:10.1530/vb-21-0009 · Cited by 21
Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors
Lenti, E., Genovese, L., Bianchessi, S., Maurizio, A., Sain, S. B., di Lillo, A., Mattavelli, G., Harel, I., Bernassola, F., Hehlgans, T., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.03.002 · Cited by 22
Peripheral Pathways to Neurovascular Unit Dysfunction, Cognitive Impairment, and Alzheimer’s Disease
Nelson, A. R. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.858429 · Cited by 24
“For example, RNAseq studies from the Betsholtz lab in mice2 (He et al., 2018; Vanlandewijck et al., 2018) and from the Human Protein Atlas in humans show that MAPT gene is expressed”
BackgroundMethodProtrudin regulates FAK activation, endothelial cell migration and angiogenesis
Arora, A., Kivelä, A. M., Wang, L., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04251-z · Cited by 21
“For isolation of ECs from mice cerebrum, cells were isolated using the Neural Tissue Dissociation Kit (P) and Myelin Removal Beads II (Miltenyi Biotec, Bergisch Glad-bach, GE), as described previously [37, 38].”
MethodSingle-cell RNA-sequencing of mammalian brain development: insights and future directions
Vinsland, E., & Linnarsson, S. (2022) · Development · doi:10.1242/dev.200180 · Cited by 21
Ha, J. M., Jin, S. Y., Lee, H. S., Kum, H. J., Vafaeinik, F., Ha, H. K., Song, S. H., Kim, C. D., & Bae, S. S. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00819-8 · Cited by 21
Reagan, A. M., Christensen, K. E., Graham, L. C., Bedwell, A. A., Eldridge, K., Speedy, R., Figueiredo, L. L., Persohn, S. A., Bottiglieri, T., Nho, K. T., et al. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221122644 · Cited by 22
“63,64 These data support a complex role for MTHFR in the brain, potentially independent of previously established peripheral/systemic roles.”
Sun, J., Qiu, J., Yang, Q., Ju, Q., Qu, R., Wang, X., Wu, L., & Xing, L. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1010392 · Cited by 25
“When combined with our scRNA-seq data, this suggests that Vas-2 deficiency as a supporting cell may play a role in the vascular defects seen in SMA mice [21, 51, 52].”
BackgroundResultEndothelial cell diversity: the many facets of the crystal
Pérez, L., Li, P., & Ferrara, N. (2022) · FEBS Journal · doi:10.1111/febs.16660 · Cited by 22
“A molecular atlas of cell types in the brain vasculature has also been developed, both under physiological and pathological conditions such as cerebral cavernous malformations (CCM) [99,100].”
Vascular endothelial cells: a fundamental approach for brain waste clearance
Wei, H., Jiang, H., Zhou, Y., Xiao, X., Zhou, C., & Ji, X. (2022) · Brain · doi:10.1093/brain/awac495 · Cited by 20
Iwao, T., Takata, F., Matsumoto, J., Goto, Y., Aridome, H., Yasunaga, M., Yokoya, M., Kataoka, Y., & Dohgu, S. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.01.037 · Cited by 21
Huang, B. B., Fukuyama, H., Burns, S. A., et al. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.320169 · Cited by 21
“9,25,40,41 A recent review of brain VMCs proposed that morphology and location of these cells be used as defining features, where arterioles and venules are surrounded by SMCs, while ensheathing pericytes and capillary pericytes surround the arteriole-capillary transition and capillaries,…”
BackgroundNetzahualcoyotzi, C., Santillán‐Cigales, J. J., Adalid-Peralta, L. V., & Velasco, I. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16106 · Cited by 24
“This web is made up of different segments: pial arterioles, penetrating arterioles, pre-capillary arterioles, and capillary and ascending venules (Coelho-Santos & Shih, 2020 ; Kaplan et al., 2020 ), each of them with a distinct composition of cell types (Vanlandewijck et al., 2018 ).”
Luo, H., Saubaméa, B., Chasseigneaux, S., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.578514 · Cited by 21
Meprin β: A novel regulator of blood–brain barrier integrity
Gindorf, M., Storck, S. E., Ohler, A., Scharfenberg, F., Becker-Pauly, C., & Pietrzik, C. U. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20905206 · Cited by 21
“This result demonstrates the specificity of Mep1b cleavage, since only one of the potential cleavage sites was readily detected and processed by Mep1b.”
BackgroundRajan, A. M., Rosin, N. L., Labit, E., Biernaskie, J. A., Liao, S., & Huang, P. (2023) · Science Advances · doi:10.1126/sciadv.adi5771 · Cited by 20
The TMEM16A channel as a potential therapeutic target in vascular disease
Al‐Hosni, R., Kaye, R. J., Choi, C. S., & Tammaro, P. (2024) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000967 · Cited by 22
“…by (i) pharmacological treatments (e.g. with diuretics acting on NKCC1), (ii) different degrees of expression, inferred from RNAseq studies [29,30], of the active transport mechanisms (see above) involved in chloride uptake in vascular cells or (iii) circadian control of NKCC1 activity […”
BackgroundOligodendrocyte-derived laminin-γ1 regulates the blood-brain barrier and CNS myelination in mice
Kang, M., & Yao, Y. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114123 · Cited by 22
The blood–brain barrier as a treatment target for neurodegenerative disorders
Rust, R., Sagare, A. P., Zhang, M., Zloković, B. V., & Kisler, K. (2025) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2025.2480654 · Cited by 21
“The identification and clustering (grouping of cells by genomic marker expression profiles) of human cell types was based on previously established vascular and perivascular markers obtained from single-cell mouse studies [10,12].”
Brain Distribution of Drugs: Pharmacokinetic Considerations
Loryan, I., Hammarlund‐Udenaes, M., & Syvänen, S. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_405 · Cited by 23
Progress in mimicking brain microenvironments to understand and treat neurological disorders
Ngo, M. T., & Harley, B. A. C. (2021) · APL Bioengineering · doi:10.1063/5.0043338 · Cited by 21
Smith-Cohn, M., Burley, N. B., & Grossman, S. A. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20999220131163504 · Cited by 21
“in 2018, could provide valuable information for understanding the viability of select VAPs dependent on expressed target receptors [154].”
Patel, N., Rajan, K. C., Blanks, A., Li, Y., Prieto, M. C., & Meadows, S. M. (2022) · JCI Insight · doi:10.1172/jci.insight.154379 · Cited by 24
Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation
Biswas, S., Shahriar, S., Giangreco, N., Arvanitis, P., Winkler, M., Tatonetti, N. P., Brunken, W. J., Cutforth, T., & Agalliu, D. (2022) · Development · doi:10.1242/dev.200610 · Cited by 19
Enström, A., Carlsson, R., Özen, Í., et al. (2022) · Biology Open · doi:10.1242/bio.059371 · Cited by 20
“Pericytes typically express S1PR1, S1PR2 and S1PR3 (He et al., 2018; Uemura et al., 2020; Vanlandewijck et al., 2018).”
Daoud, F., Arévalo‐Martínez, M., Holst, J., Holmberg, J., Albinsson, S., & Swärd, K. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115307 · Cited by 20
Mészáros, M., Phan, T. H. M., Vigh, J. P., Porkoláb, G., Kocsis, A. E., Páli, E. K., Polgár, T. F., Walter, F. R., Bolognin, S., Schwamborn, J. C., et al. (2023) · Cells · doi:10.3390/cells12030503 · Cited by 21
Spitzer, D. E., Khel, M. I., Pütz, T., Zinke, J., Jia, X., Sommer, K., Filipski, K., Thorsen, F., Freiman, T. M., Günther, S., et al. (2023) · Nature Protocols · doi:10.1038/s41596-023-00805-y · Cited by 20
“A comparative analysis for genes expressed in pericytes and expressed at low levels in the group comprising all other mural cells (vSMC, aaSMC, aSMC and fibroblasts) using the database published in Vanlandewijck et al.(18) revealed Nodal and Uchl1 as top genes.”
BackgroundMethodInfluentialUnique features of the arterial blood–brain barrier
Bell, B., Anzi, S., Sasson, E., & Ben‐Zvi, A. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00450-3 · Cited by 21
“Emerging evidence of endothelial heterogeneity across CNS vessel types [7] prompted us to investigate barrier properties of CNS arterial walls.”
BackgroundSingle Cell Gene Expression to Understand the Dynamic Architecture of the Heart
Massaia, A., Cháves, P., Samari, S., Miragaia, R. J., Meyer, K. B., Teichmann, S. A., & Noseda, M. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00167 · Cited by 20
“a punctuated pattern for mural ones (165).”
ResultMajor, M., Freund, M. K., Burch, K. S., Mancuso, N., Ng, M., Furniss, D., Paşaniuc, B., & Ophoff, R. A. (2019) · Genetic Epidemiology · doi:10.1002/gepi.22209 · Cited by 22
PRL-2 phosphatase is required for vascular morphogenesis and angiogenic signaling
Poulet, M., Sirois, J., Boyé, K., Uetani, N., Hardy, S., Daubon, T., Dubrac, A., Tremblay, M. L., & Bikfalvi, A. (2020) · Communications Biology · doi:10.1038/s42003-020-01343-z · Cited by 23
Guo, J., Yang, T., Zhang, W., Yu, K., Xu, X., Li, W., Song, L., Gu, X., Cao, R., & Cui, S. (2024) · iScience · doi:10.1016/j.isci.2024.108935 · Cited by 23
“5,6 Following SCI, the fibroblasts proliferate, migrate, and accumulate in the core area from the third day, increasing remarkably on the fifth day, and reaching their peak on the seventh day.”
BackgroundThe interactions between energy homeostasis and neurovascular plasticity
Chen, B., de Launoit, E., Meseguer, D., García‐Cáceres, C., Eichmann, A., Renier, N., & Schneeberger, M. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01021-8 · Cited by 21
Hu, K., Yin, W., Bai, Y., Zhang, J., Yin, J., Zhu, Q., & Mu, Y. (2024) · Biosensors · doi:10.3390/bios14080367 · Cited by 20
Kocsis, A. E., Kucsápszky, N., Santa-Maria, A. R., Hunyadi, A., Deli, M. A., & Walter, F. R. (2025) · Nutrients · doi:10.3390/nu17050766 · Cited by 21
“…transporters (CNTs), organic anion transporters (OATPs), and monocarboxylate transporters (MCTs), are highly expressed at the BBB, as demonstrated by transcriptomic studies on mouse [168–170] and human [171,172] isolated brain microvessels, and also on cultured brain endothelial cells [173–176].”
The rise of pericytes in neurovascular research
Beard, D. J., Brown, L. S., & Sutherland, B. A. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20958497 · Cited by 18
“Recent advances in single cell RNA sequencing analysis combined with immunofluorescence and morphological analysis have identified abcc9 (Sulfonylurea Receptor 2) and kcnj8 (Potassium Inwardly Rectifying Channel Subfamily J Member 8) as specific brain capillary pericyte markers.(50) However, the expression of these ma…”
MethodNwafor, D. C., Brichacek, A. L., Ali, A., & Brown, C. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105257 · Cited by 22
Understanding the Adult Mammalian Heart at Single-Cell RNA-Seq Resolution
Marín‐Sedeño, E., de Morentin, X. M., Pérez-Pomares, J. M., Gómez-Cabrero, D., & Ruiz‐Villalba, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645276 · Cited by 18
Ascensión, A. M., Araúzo-Bravo, M. J., & Izeta, A. (2022) · Life · doi:10.3390/life12010067 · Cited by 19
Leonard, E. V., Figueroa, R. J., Bussmann, J., Lawson, N. D., Amigo, J. D., & Siekmann, A. F. (2022) · Development · doi:10.1242/dev.199640 · Cited by 18
Endocytosis of insulin at the blood-brain barrier
Pemberton, S., Galindo, D. C., Schwartz, M. W., Banks, W. A., & Rhea, E. M. (2022) · Frontiers in Drug Delivery · doi:10.3389/fddev.2022.1062366 · Cited by 19
“The BBB is present in arterioles, capillaries, and venules throughout the brain, differentially expressing a wide range of genes based on anatomical axis, recently described as cellular zonation (Vanlandewijck et al., 2018).”
BackgroundNakajima, H., Ishikawa, H., Yamamoto, T., Chiba, A., Fukui, H., Sako, K., Fukumoto, M., Mattonet, K., Kwon, H.-B., Hui, S. P., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2022.12.013 · Cited by 18
Self-citationFibroblasts: New players in the central nervous system?
Duan, L., & Yu, X. (2023) · Fundamental Research · doi:10.1016/j.fmre.2023.01.014 · Cited by 20
“Recent scRNA-seq studies have analyzed the transcriptome of CNS fi-broblasts in mice and humans [14–19] .”
BackgroundChen, W., Man, X., Zhang, Y., Yao, G., & Chen, J. (2023) · Scientific Reports · doi:10.1038/s41598-023-32351-8 · Cited by 19
Callegari, K., Dash, S., Uchida, H., Shingai, Y., Liu, C., Khodarkovskaya, A., Lee, Y., Ito, A., Lopez, A., Zhang, T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2205786120 · Cited by 19
The Role of Astrocytes and Blood–Brain Barrier Disruption in Alzheimer’s Disease
Cruz, J. V. R., Batista, C., Diniz, L. P., & Mendes, F. A. (2023) · Neuroglia · doi:10.3390/neuroglia4030015 · Cited by 20
“…level, BBB integrity is maintained by pericytes [4] that, together with the SMCs and ECs, express many different transcripts encoding a large number of transporters, receptors, active efflux pumps, ion channels, and regulatory molecules [5], whose expression patterns vary along the capillaries [6].”
BackgroundMicrovascular Mural Cells in Cancer
Östman, A., & Corvigno, S. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.10.004 · Cited by 19
GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients
Hu, X., Matsumoto, K., Jung, R. S., Weston, T. A., Heizer, P. J., He, C. H., Sandoval, N. P., Allan, C. M., Tu, Y., Vinters, H. V., et al. (2019) · eLife · doi:10.7554/elife.47178 · Cited by 19
Self-citationHansen, K. B., Staehr, C., Rohde, P. D., Homilius, C., Kim, S., Nyegaard, M., Matchkov, V. V., & Boedtkjer, E. (2020) · eLife · doi:10.7554/elife.57553 · Cited by 19
“As illustrated in Figure 1D and E, Ptprg mRNA is found in arteriolar, capillary, as well as venular endothelial cells (Kalucka et al., 2020; Vanlandewijck et al., 2018), and it remains a future task to Figure 6 continued”
BackgroundRen, Y., Shen, Y., Si, N., Fan, S., Zhang, Y., Xu, W., Shi, L., & Zhang, X. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.639935 · Cited by 21
“, 2020), expressed mainly in astrocytes (ACs) and ECs, which are the fundamental NVU components (Vanlandewijck et al., 2018).”
BackgroundInfluentialEndothelial ontogeny and the establishment of vascular heterogeneity
Stone, O. A., Zhou, B., Red‐Horse, K., & Stainier, D. Y. R. (2021) · BioEssays · doi:10.1002/bies.202100036 · Cited by 19
“BECs within capillary beds in the heart and brain are not one homogenous cell subtype, but they rather exist along a continuum between arterial and venous transcriptional states.[62,63] During development, the heart capillary plexus also contains a transcriptionally distinct”
BackgroundCells and gene expression programs in the adult human heartPreprint
Litviňuková, M., Talavera-López, C. N., Maatz, H., Reichart, D., Worth, C. L., Lindberg, E. L., Kanda, M., Polański, K., Fasouli, E. S., Samari, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.03.024075 · Cited by 19
Laminins and the blood-brain barrier
Nasrollahi, A., & Yao, Y. (2025) · Matrix Biology · doi:10.1016/j.matbio.2025.02.005 · Cited by 20
Jiang, B., Bai, F., Hu, Y., Ren, Y. T., Su, Y., Song, W., Xie, K., Wang, D., Pan, J., Liu, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59644-y · Cited by 19
Wang, Y., Jin, Y., Laviña, B., & Jakobsson, L. (2018) · Scientific Reports · doi:10.1038/s41598-018-28770-7 · Cited by 18
Self-citationAMP-activated protein kinase is a key regulator of acute neurovascular permeability
Dragoni, S., Caridi, B., Karatsai, E., Burgoyne, T., Sarker, M. H., & Turowski, P. (2021) · Journal of Cell Science · doi:10.1242/jcs.253179 · Cited by 18
Brain Vascular Microenvironments in Cancer Metastasis
Tobar, L. E., Farnsworth, R. H., & Stacker, S. A. (2022) · Biomolecules · doi:10.3390/biom12030401 · Cited by 19
“These endothelial cells were suggested to be more active in protein synthesis due to the abundance of ribosomal transcripts and were postulated to be distributed across all cellular subsets along the arteriovenous axis due to the presence of evenly distributed markers [28].”
BackgroundResultInfluentialBjørnholm, K. D., Gaudio, F. D., Li, H., Li, W., Vázquez-Liébanas, E., Mäe, M. A., Lendahl, U., Betsholtz, C., Nilsson, P., Karlström, H., et al. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100431 · Cited by 19
Self-citationThe elusive brain perivascular fibroblast: a potential role in vascular stability and homeostasis
Sosa, M. J., Shih, A. Y., & Bonney, S. K. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1283434 · Cited by 19
“The mural basement membrane is of similar composition but also includes laminin α 1 on arterioles (2, 35).”
BackgroundInfluentialPlatelet-derived growth factor signaling in pericytes promotes hypothalamic inflammation and obesity
Okekawa, A., Wada, T., Onogi, Y., Takeda, Y., Miyazawa, Y., Sasahara, M., Tsuneki, H., & Sasaoka, T. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00793-z · Cited by 18
Bar, O., Gelb, S., Atamny, K., Anzi, S., & Ben‐Zvi, A. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00188-2 · Cited by 20
Murphy, P. A., Jailkhani, N., Nicholas, S.-A. E., Rosario, A. M. D., Balsbaugh, J. L., Begum, S., Kimble, A. L., & Hynes, R. O. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314013 · Cited by 16
Diverse mechanisms regulating brain energy supply at the capillary level
Pfeiffer, T., Li, Y., & Attwell, D. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.12.010 · Cited by 21
“Defining mural cell differences in the brain vascular bed using spatial transcriptomics Although it has been suggested that all pericytes are essentially identical and lack contractile proteins [44], the current consensus, based on imaging pericyte contraction and relaxation, is that pericytes on at least the first 4…”
BackgroundDifferentiation of Brain Pericyte‐Like Cells from Human Pluripotent Stem Cell−Derived Neural Crest
Gastfriend, B. D., Stebbins, M. J., Du, F., Shusta, E. V., & Palecek, S. P. (2021) · Current Protocols · doi:10.1002/cpz1.21 · Cited by 19
“…and efforts have been made to model brain pericyte function and dysfunction using mesodermderived pericytes (Blanchard et al., 2020; Jamieson et al., 2019), pertinent differences in molecular characteristics between brain and non-brain pericytes exist (He et al., 2018; Vanlandewijck et al., 2018).”
BackgroundRole of TRP ion channels in cerebral circulation and neurovascular communication
Kuppusamy, M., Ottolini, M., & Sonkusare, S. K. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136258 · Cited by 19
Molecular signature and functional properties of human pluripotent stem cell-derived brain pericytesPreprint
Rust, R., Sagare, A. P., Kisler, K., Kim, Y., Zhang, M., Griffin, C., Wang, Y., Clementel, V. A., Shwartz, A., Fraser, S. E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.26.546577 · Cited by 18
“…iPSC-PC and the host vasculature using a proximity ligation assay (PLA), which detects protein colocalization within 40 nm proximity, with two previously described pericyte-endothelium protein-protein/ligand-receptor molecule pairs: PDGF-BB/PDGFRB 25 and vitronectin/ Integrin α5 (ITGA5) 5 ( Fig.”
Tension at the gate: sensing mechanical forces at the blood–brain barrier in health and disease
Hansen, C. E., Hollaus, D., Kamermans, A., & de Vries, H. E. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03321-2 · Cited by 21
Qiu, F., Miao, H., Hui, H., Qiu, L.-J., Chen, Y., Luo, M., Zhang, J., Lin, Y., Li, D., Ong, S., et al. (2025) · Circulation Research · doi:10.1161/circresaha.125.326173 · Cited by 22
Zeng, Z., Wang, X., Pei, J., Wang, P., Li, J., Li, F., Wang, J., Zhao, Y., Yu, C., Liu, H., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf372 · Cited by 20
Regional heterogeneity of the blood-brain barrier
Blanchette, M., Bajc, K., Gastfriend, B. D., Profaci, C. P., Ruderisch, N., Dorrier, C., Zhong, G. G., Durán, R. C., Harvey, S. S., Garcia-Pak, I. H., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61841-8 · Cited by 27
Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human
Hill, S. A., Bravo‐Ferrer, I., Čiulkinytė, A., Ramos, N. P., Rossetti, I., Colvin, C., Beltran-Lobo, P., Parra-Pérez, C., Emelianova, K., Dando, O., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65487-4 · Cited by 21
Pericytes orchestrate a tumor-restraining microenvironment in glioblastoma
Braun, S., Bolívar, P., Oudenaarden, C., Sjölund, J., Bocci, M., Harbst, K., Talkhoncheh, M. S., Phung, B., Cordero, E., Rosberg, R., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-66985-1 · Cited by 21
Novel COL4A1‐VEGFD gene fusion in myofibroma
Dachy, G., Fraitag, S., Boulouadnine, B., Cordi, S., & Demoulin, J. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16502 · Cited by 18
Kakava, S., Schlumpf, E., Panteloglou, G., Tellenbach, F. L., von Eckardstein, A., & Robert, J. (2022) · Cells · doi:10.3390/cells11193044 · Cited by 20
“There is evidence that HDL can cross the BBB and enter the brain [36].”
BackgroundInfluentialLiu, S., Li, H., Shen, Y., Zhu, W., Wang, Y., Wang, J., Zhang, N., Li, C., 余曙光, Lu⁃shuang, X., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1069155 · Cited by 16
“Screening of the AD-related AEGs A total of 204 AC marker genes were screened from the VascularSingleCells (Vanlandewijck et al., 2018) with fold change > 100 than other BBB cells.”
BackgroundSamuels, J. D., Lotstein, M. L., Lehmann, M. L., ELKAHLOUN, A. G., Banerjee, S., & Herkenham, M. A. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02827-5 · Cited by 18
Drug targeting in psychiatric disorders — how to overcome the loss in translation?
Khodosevich, K., Dragičević, K., & Howes, O. D. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00847-7 · Cited by 17
“For instance, single-cell RNA-sequencing atlases for brain vasculature in human 29 and mouse brains 107 are available that can be used to reconstruct the blood–brain barrier at the molecular and cellular levels.”
A high-resolution view of the heterogeneous aging endothelium
Dobner, S., Tóth, F., & de Rooij, L. P. M. H. (2024) · Angiogenesis · doi:10.1007/s10456-023-09904-6 · Cited by 23
“Representing one of the very first tissues for which the endothelium was profiled at single-cell resolution [17], we now have an in-depth understanding of endothelial arteriovenous zonation and the associated EC subtypes and gene expression patterns in the mouse and human brain [18, 19].”
BackgroundSex differences in the rodent medial prefrontal cortex – What Do and Don't we know?
Laine, M. A., Greiner, E. M., & Shansky, R. M. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.109867 · Cited by 18
Induced pluripotent stem cell-derived vascular smooth muscle cells
Stephenson, M. K., Reich, D. H., & Boheler, K. R. (2020) · Vascular Biology · doi:10.1530/vb-19-0028 · Cited by 18
Tissue factor pathway inhibitor is required for cerebrovascular development in mice
Maroney, S. A., Westrick, R. J., Cleuren, A. C. A., et al. (2020) · Blood · doi:10.1182/blood.2020006054 · Cited by 17
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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