The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
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
Cited by
Sorted by citations
Items 1,001–1,100 of 1,911
Pfau, S. J., Langen, U. H., Fisher, T. M., Prakash, I., Nagpurwala, F., Lozoya, R. A., Lee, W.-C. A., Wu, Z., & Gu, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.26.441465 · Cited by 13
Single-cell dissection of the human cerebrovasculature in health and diseasePreprint
García, F., Sun, N., Lee, H., Godlewski, B. R., Galani, K., Mantero, J. C., Bennett, D. A., Şahin, M., Kellis, M., & Heiman, M. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.26.440975 · Cited by 13
Reconstructing the ancestral vertebrate brain using a lamprey neural cell type atlasPreprint
Lamanna, F., Hervas-Sotomayor, F., Oel, A. P., Jandzík, D., Sobrido‐Cameán, D., Martik, M. L., Green, S. A., Brüning, T., Mößinger, K., Schmidt, J., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.28.482278 · Cited by 13
Morton, L., Garza, A. P., Dębska–Vielhaber, G., Villafuerte, L. E., Henneicke, S., Arndt, P., Meuth, S. G., Schreiber, S., & Dunay, I. R. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.124.038457 · Cited by 13
CD8 T cells as drivers of blood–brain barrier disruption
Seady, M., & Johnson, A. J. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.008 · Cited by 17
The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment
Gu, Y., & Muller, W. J. (2025) · Cancer Research · doi:10.1158/0008-5472.can-25-1486 · Cited by 17
“These findings suggest that even in solid tumors with intrinsically low CAF infiltration, OPN remains a critical factor that bridges CAF and cancer cell interaction with therapeutic potential (138, 140).”
Underly, R. G., & Shih, A. Y. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.619230 · Cited by 12
“Sodium hydroxide (1 M) was then added to bring the solution to a neutral pH. Saline was then added to bring the solution to the appropriate concentration (Wanisch and Wotjak, 2008).”
MethodRiew, T., Hwang, J.-W., Jin, X., Kim, H. L., & Lee, M. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1033271 · Cited by 11
Chen, Z., Hu, W., Valdez, M. J. M., Gossman, Z. C., Chomyk, A. M., Boylan, B. T., Kidd, G. J., Phares, T. W., Bergmann, C. C., & Trapp, B. D. (2023) · ASN NEURO · doi:10.1177/17590914221146365 · Cited by 12
“LPS binds to Toll-like receptor 4 (TLR4), which is expressed on monocytes (Chen et al., 2012), microglia (Vaure and Liu, 2014), and brain endothelial cells (Nagyoszi et al., 2010; Vanlandewijck et al., 2018); its expression on murine astrocytes has not been established (Vaure and Liu, 2014).”
BackgroundMethodResultLochhead, J. J., Williams, E. I., Reddell, E. S., Dorn, E., Ronaldson, P. T., & Davis, T. P. (2023) · Cells · doi:10.3390/cells12040645 · Cited by 14
“In larger cerebral blood vessels, such as arterioles, perivascular macrophages and fibroblasts are present and pericytes are replaced by smooth muscle cells [12,63,64].”
BackgroundMohan, K., Gasparoni, G., Salhab, A., Orlich, M. M., Geffers, R., Hoffmann, S., Adams, R. H., Walter, J., & Nordheim, A. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.031044 · Cited by 13
Dudley-Fraser, J., & Rittinger, K. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1287257 · Cited by 15
Celentano, C., Carotenuto, L., Miceli, F., Carleo, G., Corrado, B., Baroli, G., Iervolino, S., Vecchione, R., Taglialatela, M., & Barrese, V. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00709.2023 · Cited by 14
Neuroimmunology of Cardiovascular Disease
Zarate, S. M., Kirabo, A., Hinton, A. O., Jr., & Santisteban, M. M. (2024) · Current Hypertension Reports · doi:10.1007/s11906-024-01301-8 · Cited by 15
Brain Microvascular Pericyte Pathology Linking Alzheimer's Disease to Diabetes
El‐Ghazawi, K., Eyo, U. B., & Peirce, S. M. (2024) · Microcirculation · doi:10.1111/micc.12877 · Cited by 14
Miao, Y., Li, W., Jeansson, M., Mäe, M. A., Muhl, L., & He, L. (2024) · Vascular Pharmacology · doi:10.1016/j.vph.2024.107434 · Cited by 12
Self-citationNeurovascular unit in ischemic stroke in older adults: a narrative review
Wang, C., Yang, Y., Xiong, T., & Li, S. (2025) · Aging advances. · doi:10.4103/agingadv.agingadv-d-24-00031 · Cited by 16
PRDM16, a new kid on the block in cardiovascular health and disease
Wauwe, J. V., Kemps, H., Vrancaert, P., Mahy, A., Schellingen, R., Grootaert, M. O. J., Beerens, M., & Luttun, A. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf089 · Cited by 12
Resident Endothelial Progenitors Make Themselves at Home
Hirschi, K. K., & Dejana, E. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.07.014 · Cited by 12
Vascular Heterogeneity With a Special Focus on the Hepatic Microenvironment
Fleischer, J. R., Jodszuweit, C. A., Ghadimi, M. B., Oliveira, T. D., & Conradi, L. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.591901 · Cited by 12
The Oncogene Transcription Factor EB Regulates Vascular Functions
Doronzo, G., Astanina, E., & Bussolino, F. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.640061 · Cited by 12
“(Roczniak-Ferguson et al., 2012; Settembre et al., 2012; Palmieri et al., 2017; Vega-Rubin-de-Celis et al., 2017).”
BackgroundInfluentialApproaches for the isolation and long-term expansion of pericytes from human and animal tissues
Alvino, V. V., Mohammed, K. A. K., Gu, Y., & Madeddu, P. R. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1095141 · Cited by 13
He, Q., Li, X., Singh, K. N., Luo, Z., Cordova, M. M., Jamalpour, M., Lindahl, B., Křı́ž, V., Vuolteenaho, R., Ulvmar, M. H., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-44039-z · Cited by 12
Takashima, S., Watanabe, C., Ema, M., & Mizutani, K. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104481 · Cited by 12
“2A), which also regulate development of telencephalic neuroepithelial domains and post-mitotic neurons, raising the possibility that neurogenesis and angiogenesis in the neocortex may be linked mechanistically (Vasudevan et al., 2008).”
The year in review: progress in brain barriers and brain fluid research in 2018
Keep, R. F., Jones, H. C., & Drewes, L. R. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0124-y · Cited by 12
“[136] used single cell transcriptomics to examine changes in endothelial and mural cell gene expression going from arterial, capillary, to venous vessels (zonation).”
MethodNicoletti, C., Wei, X., Etxaniz, U., Proietti, D., Madaro, L., & Puri, P. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.29.424762 · Cited by 11
Endothelial Cells and the Cerebral Circulation
Lansdell, T. A., Chambers, L. C., & Dorrance, A. M. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210015 · Cited by 22
Jones, H. E., Coelho‐Santos, V., Bonney, S. K., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.23.533982 · Cited by 12
“…a fibroblast-like cell type located on the outside of the vSMC layer of large-diameter arterioles and venules, but not capillaries, in the adult mouse brain (Bonney et al., 2022; Soderblom et al., 2013; Vanlandewijck et al., 2018) and in adult human brain (Garcia et al., 2022; Yang et al., 2022).”
BackgroundInfluentialAnatomical structures, cell types, and biomarkers of the healthy human blood vasculature
Boppana, A., Lee, S., Malhotra, R. K., Halushka, M. K., Gustilo, K. S., Quardokus, E. M., Herr, B. W., Börner, K., & Weber, G. M. (2023) · Scientific Data · doi:10.1038/s41597-023-02018-0 · Cited by 14
Pizzo, M. E., Plowey, E. D., Khoury, N., Kwan, W., Abettan, J., DeVos, S. L., Discenza, C. B., Earr, T., Joy, D. A., Lye‐Barthel, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.26.604664 · Cited by 13
“…showed predominantly parenchymal distribution, greater plaque target engagement, and far less accumulation around CSF-communicating perivascular spaces, particularly for large surface arteries, consistent with reduced expression of TfR on arterial endothelial cells (Vanlandewijck et al., 2018).”
BackgroundMa, Y., Xia, Y., Karako, K., Song, P., Tang, W., & Hu, X. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04997-0 · Cited by 13
“Neurovascular dysfunction is a contributing factor to the pathogenesis of various neurodegenerative diseases, including AD [91, 92].”
Phased blood-brain barrier disruption in ischaemic stroke: implications for therapy?
Blase, A., di Girasole, C. G., Benjamin, L. A., & Turowski, P. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-025-00701-5 · Cited by 15
“When analysed by sc-RNAseq both CLDN11 [58] and CLDN25 [57] are detected at significant levels in ECs in addition to CLDN5.”
Choi, J. P., Yang, X., He, S., Song, R., Xu, Z., Foley, M., Wong, J. J. L., Xu, C., & Zheng, X. (2021) · Stroke · doi:10.1161/strokeaha.120.031523 · Cited by 12
Wu, X., Li, J., Fu, Y., Chen, D., Nie, H., & Tang, Z. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.369099 · Cited by 11
Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord
Kim, H., Skuba, A., Xia, J., Han, S. B., Zhai, J., Hu, H., Kang, S. H., & Son, Y. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113068 · Cited by 11
Yan, Y., Truitt, B., Tao, J., Boyles, S. M., Antoine, D., Hulme, W. F., & Roy, S. (2023) · iScience · doi:10.1016/j.isci.2023.108166 · Cited by 14
Decoding fibrosis in the human central nervous system
Holl, D., & Göritz, C. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00243.2023 · Cited by 12
Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction
Tung, L. W., Groppa, E., Soliman, H., Lin, B., Chang, C.-K., Cheung, C. W., Ritso, M., Guo, D., Rempel, L., Sinha, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-44227-6 · Cited by 12
Gaceb, A., Roupé, L., Enström, A., et al. (2024) · Stroke · doi:10.1161/strokeaha.123.045720 · Cited by 11
“23 In addition, the identified microvesicle cargo is comparable to the proteome of brain pericytes described previously in vitro, which is why we think other cell types have had a minimal effect on the analysis.”
ResultZavvarian, M.-M., Modi, A. D., Sadat, S., Hong, J., & Fehlings, M. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115708 · Cited by 12
“These cells are supported by a variety of glial and vascular cells, including astrocytes, oligodendrocytes, microglia, fibroblasts, pericytes, endothelial cells, and smooth muscle cells [6–8].”
BackgroundQu, X., Yang, R., Tan, C., Chen, H., & Wang, X. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04303-4 · Cited by 10
“For example, ROR1 is expressed in human BMECs, but almost not in mouse brain capillary ECs [48].”
Zhou, H., Neudecker, V., Perez‐Zoghbi, J. F., Brambrink, A. M., & Yang, G. (2024) · Communications Biology · doi:10.1038/s42003-024-07200-7 · Cited by 11
Endothelial response to blood-brain barrier disruption in the human brain
Gould, A., Luan, Y., Hou, Y., Korobova, F. V., Chen, L., Arrieta, V. A., Amidei, C., Ward, R., Gomez, C., Castro, B. A., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.187328 · Cited by 14
Protzmann, J., Zeitelhofer, M., Stefanitsch, C., Torrente, D., Adzemovic, M. Z., Matjunins, K., Randel, S. J. I., Lewandowski, S. A., Muhl, L., Eriksson, U., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci171077 · Cited by 11
Unraveling the transcriptomic landscape of brain vascular cells in dementia: A systematic review
Sewell, M. D. E., Fialova, N., & Montagne, A. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14512 · Cited by 13
“9,10 Indeed, several studies utilizing single-nuclear RNA-sequencing (snRNA-seq) of vascular cells from postmortem tissues of patients with dementia and various neurodegenerative disorders have demonstrated that vascular dysfunction is closely linked to extensive transcriptomic alterations…”
An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
Zhang, Z., Cheng, H., Yang, Z., Deng, X., Kang, M., Qiu, P. S., Wang, K., Wang, D., & Tang, B. Z. (2025) · Aggregate · doi:10.1002/agt2.70055 · Cited by 11
Adnani, L., Meehan, B., Kim, M., Choi, D., Rudd, C. E., Riazalhosseini, Y., & Rak, J. W. (2025) · Science Advances · doi:10.1126/sciadv.adr6940 · Cited by 12
“This may, at least in part, result from zonation of the vascular system in the brain ( 78 ) or from the influence of the tumor microenvironment that may trigger phenotypic and molecular anomalies ( 38 ).”
Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration
Spears, L. D., Adak, S., Dong, G., Wei, X., Spyropoulos, G., Zhang, Q., Li, Y., Chu, F., Hu, D., Lodhi, I. J., et al. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100079 · Cited by 14
“Individual neurons are usually closer to a brain capillary than a CSF compartment (65), making it likely that the heterogeneous brain capillary endothelium (78) influences the neural microenvironment.”
BackgroundCleuren, A. C. A., & Molema, G. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1252021 · Cited by 13
Network response of brain microvasculature to neuronal stimulation
Mester, J. R., Rozak, M. W., Dorr, A. E., Goubran, M., Sled, J. G., & Stefanovic, B. (2024) · NeuroImage · doi:10.1016/j.neuroimage.2024.120512 · Cited by 12
“The higher α smooth muscle actin expression on precapillary arterioles is a clear indicator of the distinctions between them and capillaries (Vanlandewijck et al., 2018), and supportive of their role in local blood flow redistribution on a fine spatial scale (Itoh and Suzuki, 2012; Fern ´…”
Ziegler, T., Bähr, A., Howe, A., Klett, K., Husada, W., Weber, C., Laugwitz, K., Kupatt, C., & Hinkel, R. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.06.004 · Cited by 11
Pericytes in Hereditary Hemorrhagic Telangiectasia
Galaris, G., Thalgott, J. H., & Lebrin, F. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-16908-4_10 · Cited by 12
Hsu, C. Y., Gomez-Salazar, M. A., Miller, S., Meyers, C. A., Ding, C., Hardy, W. R., Péault, B., & James, A. W. (2019) · Stem Cells and Development · doi:10.1089/scd.2019.0106 · Cited by 11
“Among these 229 proteins (Supplementary Table S2), well-known pericyte markers ENG, Myl9 [12] have been reported to be associated with pericytes.”
BackgroundDikshit, A., Zong, H., Anderson, C. M., Zhang, B., & Ma, X. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0623-0_19 · Cited by 12
Cerebrovascular development: mechanisms and experimental approaches
Chico, T., & Kugler, E. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03790-1 · Cited by 12
Shedding Light on the Blood–Brain Barrier Transport with Two-Photon Microscopy In Vivo
Kucharz, K., Kutuzov, N. P., Zhukov, O., Janiurek, M. M., & Lauritzen, M. (2022) · Pharmaceutical Research · doi:10.1007/s11095-022-03266-2 · Cited by 12
“The fact that S1PR1 is mostly expressed in arterioles (104) and that S1PR1-dependent increase also occurred in arterioles, but not in venules or capillaries (98), may indicate that the transcytosis is differentially regulated along the vascular tree.”
BackgroundKim, H.-B., Lu, Y., Oh, S. C., Morris, J. F., Miyashiro, K., Kim, J., Eberwine, J. H., & Sul, J. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102147 · Cited by 11
Betsholtz, C. (2022) · Upsala Journal of Medical Sciences · doi:10.48101/ujms.v127.9051 · Cited by 12
Self-citationWang, M., & Zhou, H. J. (2022) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041188 · Cited by 13
Brain and blood single-cell transcriptomics in acute and subacute phases after experimental strokePreprint
García‐Bonilla, L., Shahanoor, Z., Sciortino, R. K., Nazarzoda, O., Racchumi, G., Iadecola, C., & Anrather, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.31.535150 · Cited by 12
Hypertension-induced neurovascular and cognitive dysfunction at single-cell resolution
Schaeffer, S. M., Pacholko, A. G., Santisteban, M. M., Ahn, S. J., Racchumi, G., Wang, G., Park, L., Faraco, G., Anrather, J., & Iadecola, C. (2025) · Neuron · doi:10.1016/j.neuron.2025.10.018 · Cited by 14
Molecular Heterogeneity of the Brain Endothelium
Alnaqbi, N., Mohammad, M. G., Hamoudi, R., Mabondzo, A. M., & Harati, R. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45040227 · Cited by 12
Shireman, J. M., Cheng, L., Goel, A., Garcia, D. P. M., Partha, S., Quiñones‐Hinojosa, A., Kendziorski, C. M., & Dey, M. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1266397 · Cited by 13
“…embryonal development, brain undergoes complex developmental patterning for separation of central nervous system (CNS) and peripheral nervous system (PNS) as well as the development and migration of cells throughout the cerebral cortex ranging from axon guidance to synapse formation (4, 10 – 13).”
BackgroundAvila‐Gutierrez, K., Slaoui, L., Alvear‐Perez, R., Kozlowski, E., Oudart, M., Augustin, E., Claveau, C., Mailly, P., Monnet, H., Mignon, V., et al. (2024) · Glia · doi:10.1002/glia.24503 · Cited by 9
“To address this hypothesis, we focused on mRNAs that are selectively or specifically expressed in astrocytes, according to published single-cell RNASeq datasets (He et al., 2016; Vanlandewijck et al., 2018; Zeisel et al., 2015).”
MethodResultInfluentialLi, Y., Zhou, L., Deng, H., Zhang, Y., Li, G., Yu, H.-F., Wu, K., & Wang, F. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00380 · Cited by 10
Hobara, T., Higuchi, Y., Yoshida, M., Suehara, M., Ando, M., Yuan, J., Yoshimura, A., Kojima, F., Matsuura, E., Okamoto, Y., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01847-3 · Cited by 10
“The expression levels of MYORG RNA in the adult mouse and human brain were assessed using single-cell RNA-seq data from (http://betsholtzlab.org/VascularSingl-eCells/database.html) [16, 41] and (https://twc-stanford. shinyapps.io/human_bbb/) [44].”
MethodPericyte ablation causes hypoactivity and reactive gliosis in adult mice
Cashion, J. M., Brown, L. S., Morris, G. P., Fortune, A. J., Courtney, J., Makowiecki, K., Premilovac, D., Cullen, C. L., Young, K. M., & Sutherland, B. A. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.10.014 · Cited by 10
“2I). α SMA is more highly expressed by VSMCs than pericytes in vivo (Smyth et al., 2018b, Vanlandewijck et al., 2018).”
BackgroundInfluentialGlucagon‐Like Peptide‐1 Links Ingestion, Homeostasis, and the Heart
Krieger, J., Daniels, D., Lee, S. J., Mastitskaya, S., & Langhans, W. (2024) · Comprehensive physiology · doi:10.1002/cph4.7 · Cited by 14
“This arteriolar presence has also been confirmed in a single-cell RNA sequencing study of the brain vasculature (Vanlandewijck et al. 2018).”
Al‐Hosni, R., Agostinelli, E., Ilkan, Z., Scofano, L. F., Kaye, R., Dinsdale, R. L., Acheson, K. E., MacDonald, A., Rivers, D. A., Biosa, A., et al. (2025) · British Journal of Pharmacology · doi:10.1111/bph.17383 · Cited by 11
“…described above are unlikely to be indirect consequence of modulation of the electrical activity in cortical neurons in the vicinity of the imaged pericytes because TMEM16A is not expressed in pyramidal cortical neurons (Vanlandewijck et al., 2018; Ximerakis et al., 2019; Zeisel et al., 2018).”
Pericyte Electrical Signalling and Brain Haemodynamics
Longden, T. A., & Isaacs, D. P. (2025) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70030 · Cited by 12
“…are composed of a molecularly-distinct set of ECs that organize into a continuum with varying gene expression along the arterio-venous axis [15–17], and their abluminal surface is decorated by the cell bodies and processes of pericytes, which may be divided into the major categories of…”
InfluentialZhao, N., Pessell, A. F., Chung, T. D., & Searson, P. C. (2025) · Matrix Biology · doi:10.1016/j.matbio.2025.04.003 · Cited by 10
Pericyte-glial cell interactions: Insights into brain health and disease
Sepehrinezhad, A., & Gorji, A. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01472 · Cited by 12
“Pericytes express several laminins, including laminin-α2, laminin-γ1, and laminin-β1, which collectively form laminin 211 in the basement membrane, playing a key role in vascular stability and the integrity of the NVU (Gautam et al., 2016; Vanlandewijck et al., 2018).”
Kimble, A. L., Silva, J., Omar, O. M., Murphy, M. D., Hensel, J. A., Nicholas, S.-A. E., Jellison, E. R., Reese, B., & Murphy, P. A. (2021) · Laboratory Investigation · doi:10.1038/s41374-021-00698-z · Cited by 11
Rajagopalan, N. R., Vista, W.-R., Fujimori, M., Vroomen, L. G. P. H., Jiménez, J. M., Khadka, N., Bikson, M., & Srimathveeravalli, G. (2023) · Annals of Biomedical Engineering · doi:10.1007/s10439-023-03211-3 · Cited by 10
“The BBB supports a healthy brain by regulating the transport of nutrients and waste products protecting the brain from pathogens and inflammation [39, 40].”
BackgroundHamada, Y., Ogata, S., Masuda, T., et al. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00449-w · Cited by 10
“P-glycoprotein is an efflux transporter selectively expressed in BCECs and limits drug entry into the brain [3].”
MethodInfluentialHolst, M. R., de Wit, N. M., Ozgür, B., Brachner, A., Hyldig, K., Appelt‐Menzel, A., Sleven, H., Cader, M. Z., de Vries, H. E., Neuhaus, W., et al. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00480-x · Cited by 12
“The cell surface localized receptors CD133 (Gene: PROM1 ) and podocalyxin (Gene: PODXL ) are highly expressed in brain endothelial cells [33, 39, 43].”
BackgroundStefanakis, N., Jiang, J., Liang, Y., & Shaham, S. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00049-w · Cited by 11
“While FoxF genes are expressed only at low levels in microglia (Vanlandewijck et al, 2018), it remains possible that these genes direct early microglia differentiation.”
The solute carrier SLC7A1 may act as a protein transporter at the blood-brain barrier
Kurtyka, M., Wessely, F., Bau, S. S., Ifie, E., He, L., de Wit, N. M., Pedersen, A. B. V., Keller, M., Webber, C., de Vries, H. E., et al. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151406 · Cited by 12
Self-citationQuantifying Ca2+ signaling and contraction in vascular pericytes and smooth muscle cells
Halaidych, O. V., Mummery, C. L., & Orlova, V. V. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.03.143 · Cited by 10
Sharpening the tools for pericyte research
Berthiaume, A., & Shih, A. Y. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0437-9 · Cited by 10
Foley, K. E., Yang, H. S., Graham, L. C., & Howell, G. R. (2019) · BMC Genomics · doi:10.1186/s12864-019-6230-z · Cited by 9
Tau reduction in aged mice does not impact Microangiopathy
Bennett, R. E., Hu, M., Fernandes, A. R., Pérez-Rando, M., Robbins, A. B., Kamath, T. V., Dujardin, S., & Hyman, B. T. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01014-4 · Cited by 11
Wang, J., Deng, X., Xie, Y., Tang, J., Zhou, Z., Yang, F., He, Q., Cao, Q., Zhang, L., & He, L. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2020.599834 · Cited by 12
Self-citationA Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms
Segawa, K., Blumenthal, Y., Yamawaki, Y., & Ohtsuki, G. (2021) · Biology · doi:10.3390/biology10010034 · Cited by 11
“Therefore, a lot of attention is paid to the fact that brain inflammation, lymphedema, aberrant immunity, hypertension, and obesity result in various alterations in the vascular and lymphatic systems, such as leakage, damage, cleavage, hypo- and hyper-plasia [19,20].”
BackgroundThe human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factorsPreprint
Ghobrial, M., Charish, J., Takada, S., Valiante, T. A., Monnier, P. P., Radovanovic, I., Bader, G. D., & Wälchli, T. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.10.334664 · Cited by 10
“Lancet 395, 497-506, doi:10.1016/S0140-6736(20)30183-5 (2020). 38 Walchli, T.”
InfluentialKoehn, L. M. (2021) · Springer eBooks · doi:10.1007/978-3-030-51519-5_76-1 · Cited by 10
Modeling Brain Vasculature Immune Interactions In VitroPreprint
Lyck, R., Nishihara, H., Aydin, S., Soldati, S. G., & Engelhardt, B. (2022) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041185 · Cited by 10
Huang, Y., Wu, G., Bi, G., Cheng, L., Liang, J., Li, M., Zhang, H., Shan, G., Hu, Z., Chen, Z., et al. (2024) · eLife · doi:10.7554/elife.95988 · Cited by 10
Torres, V. O., Pizzo, M. E., Chan, D., Dugas, J. C., Huynh, D., Joy, D. A., Liang, E., Sarrafha, L., Becerra, I. A., Chau, R., et al. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251361997 · Cited by 13
“56 In order to evaluate TfR protein and its distribution along the cerebrovasculature, we extended our multiplex imaging platform to qualitatively assess vascular TfR in AD versus control human frontal cortex.”
Development of the blood–brain barrier
Gastfriend, B. D., & Daneman, R. (2026) · Development · doi:10.1242/dev.205134 · Cited by 17
“Many BBB-associated genes, such as Tfrc , Mfsd2a and Vcam1 , display zonated expression (Jeong et al., 2022; Vanlandewijck et al., 2018).”
InfluentialStrategies for blood–brain barrier rejuvenation and repair
Searson, P. C., & Banks, W. A. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01364-5 · Cited by 15
Molecular landscape and emerging therapeutic strategies in breast cancer brain metastasis
Xiong, S., Tan, X., Wu, X., Wan, A., Zhang, G., Wang, C., Liang, Y., & Zhang, Y. (2023) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359231165976 · Cited by 9
“51 Although the structure is damaged, a BTB can impede the transport of anticancer medicines to brain tumors, leading to poor treatment results.”
BackgroundCerebral venous impairment and cerebral venous sinus thrombosis
Wang, J., Manaenko, A., Hu, Q., & Zhang, X. (2024) · Brain Hemorrhages · doi:10.1016/j.hest.2024.03.002 · Cited by 10
Grand, Q. L., Tsuchida, A., Koch, A., Imtiaz, M. A., Aziz, N. A., Vigneron, C., Zago, L., Lathrop, M. G., Dubrac, A., Couffinhal, T., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02604-7 · Cited by 16
Jiang, Y., Bei, W.-X., Li, W., Huang, Y., He, S., Zhu, X., Zheng, L., Xia, W., Dong, S., Liu, Q., et al. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.70061 · Cited by 10
Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis
Llaó-Cid, C., Peguera, B., Kobialka, P., Decker, L., Vogenstahl, J., Alivodej, N., Srivastava, S., Jin, J., Kirchmaier, B. C., Milla, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54570-x · Cited by 10
BBB breakdown caused by plasma membrane pore formation
Wei, C., Jiang, W., Luo, M., & Shao, F. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.02.012 · Cited by 11
Xing, M., Liang, S., Cao, W., et al. (2025) · Advanced Science · doi:10.1002/advs.202416904 · Cited by 9
Solders, S. K., Shen, Q., & Reas, E. T. (2025) · NeuroImage Clinical · doi:10.1016/j.nicl.2025.103805 · Cited by 8
“…matter K trans from APOE4. explored BBB heterogeneity through gene expression or cellular composition along the arteriole-capillary-venule axis (Vanlandewijck et al., 2018; Kalucka et al., 2020), few have examined anatomical variation, and those that have focused on select brain regions (Yang…”
A comprehensive molecular atlas of the mesenchymal cell types in the mouse liver
Pietilä, R. S., Genové, G., Mocci, G., Miao, Y., Liu, J., Leptidis, S., Gaudio, F. D., Uhrbom, M., Vázquez-Liébanas, E., Gustafsson, S., et al. (2025) · EMBO Reports · doi:10.1038/s44319-025-00580-9 · Cited by 18
“Peribiliary pericytes also morphologically resemble pericytes found in other tissues (Armulik et al, 2011; Muhl et al, 2020; Vanlandewijck et al, 2018) (Fig.”
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
