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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
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
Molecular Architecture of the Mouse Nervous System
Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L. E., La Manno, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.021 · Cited by 2,552
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
“The first stage of analysis robustly grouped cells into 8–11 broad classes (Data S2), including neurons, astrocytes, microglia/macrophages, oligodendrocytes, polydendrocytes (oligodendrocyte progenitor cells), and components of the vasculature—endothelial cells, fibroblast-like cells, andmural cells (Abbott et al., 20…”
BackgroundResultInfluentialBlood–brain barrier breakdown is an early biomarker of human cognitive dysfunction
Nation, D. A., Sweeney, M. D., Montagne, A., Sagare, A. P., D’Orazio, L. M., Pachicano, M., Sepehrband, F., Nelson, A. R., Buennagel, D. P., Harrington, M. G., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0297-y · Cited by 1,728
The blood–brain barrier and blood–tumour barrier in brain tumours and metastases
Arvanitis, C., Ferraro, G. B., & Jain, R. K. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0205-x · Cited by 1,919
Cells of the adult human heart
Litviňuková, M., Talavera-López, C., Maatz, H., Reichart, D., Worth, C. L., Lindberg, E. L., Kanda, M., Polanski, K., Heinig, M., Lee, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2797-4 · Cited by 1,729
Single-Cell Transcriptome Atlas of Murine Endothelial Cells
Kalucka, J. M., de Rooij, L. P. M. H., Goveia, J., Rohlenová, K., Dumas, S. J., Meta, E., Conchinha, N. V., Taverna, F., Teuwen, L.-A. M. N., Veys, K., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.015 · Cited by 1,356
Peng, J., Sun, B.-F., Chen, C.-Y., Zhou, J.-Y., Chen, Y.-S., Chen, H., Liu, L., Huang, D., Jiang, J., Cui, G.-S., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0195-y · Cited by 1,321
Kim, N., Kim, H. K., Lee, K., Hong, Y., Cho, J. H., Choi, J. W., Lee, J.-I., Suh, Y., Ku, B. M., Eum, H. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16164-1 · Cited by 1,309
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Yao, Z., van Velthoven, C. T. J., Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06812-z · Cited by 1,203
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Terstappen, G. C., Meyer, A. H., Bell, R. D., & Zhang, W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00139-y · Cited by 1,138
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Sweeney, M. D., Kisler, K., Montagne, A., Toga, A. W., & Zlokovic, B. V. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0234-x · Cited by 998
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Aldape, K., Brindle, K. M., Chesler, L., Chopra, R., Gajjar, A., Gilbert, M. R., Gottardo, N., Gutmann, D. H., Hargrave, D., Holland, E. C., et al. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0177-5 · Cited by 959
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Ximerakis, M., Lipnick, S. L., Innes, B. T., Simmons, S. K., Adiconis, X., Dionne, D., Mayweather, B. A., Nguyen, L., Niziolek, Z., Ozek, C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0491-3 · Cited by 736
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Iadecola, C., Duering, M., Hachinski, V., Joutel, A., Pendlebury, S. T., Schneider, J. A., & Dichgans, M. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.04.034 · Cited by 865
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797
Self-citationThe blood–brain barrier in health and disease: Important unanswered questions
Profaci, C. P., Munji, R. N., Pulido, R. S., & Daneman, R. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190062 · Cited by 811
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Rustenhoven, J., Drieu, A., Mamuladze, T., de Lima, K. A., Dykstra, T., Wall, M., Papadopoulos, Z., Kanamori, M., Salvador, A. F., Baker, W., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.040 · Cited by 685
“Consistent with previous studies on CNS vasculature (Vanlandewijck et al., 2018), brain stromal sequencing was largely comprised of Pecam1+ endothelial cells with capillary (cECs; Tfrchi), arterial (aECs; Bmxhi), or venous (vECs; Trfclo, Bmxlo, Vwfhi) zonation markers and high expression of…”
InfluentialMuhl, L., Genové, G., Leptidis, S., Liu, J., He, L., Mocci, G., Sun, Y., Gustafsson, S., Buyandelger, B., Chivukula, I. V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17740-1 · Cited by 684
“8b, c, Supplementary Data 10) and likely represent SMC from the heart ’ s large vessel outlets, i.e., the pulmonary trunk and aorta 49,50 .”
InfluentialSelf-citationRevisiting the neurovascular unit
Schaeffer, S. M., & Iadecola, C. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00904-7 · Cited by 699
Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2021) · Physiological Reviews · doi:10.1152/physrev.00031.2020 · Cited by 642
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Chen, R., Wang, K., Yu, J., Howard, D., French, L., Chen, Z., Wen, C., & Xu, Z. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.573095 · Cited by 570
Molecular architecture of the developing mouse brain
La Manno, G., Siletti, K., Furlan, A., Gyllborg, D., Vinsland, E., Mossi Albiach, A., Mattsson Langseth, C., Khven, I., Lederer, A. R., Dratva, L. M., et al. (2021) · Nature · doi:10.1038/s41586-021-03775-x · Cited by 563
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Wei, K., Korsunsky, I., Marshall, J. L., Gao, A., Watts, G. F. M., Major, T., Croft, A. P., Watts, J., BLAZAR, P. E., Lange, J. K., et al. (2020) · Nature · doi:10.1038/s41586-020-2222-z · Cited by 536
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Trimm, E., & Red-Horse, K. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00770-1 · Cited by 537
Development and Cell Biology of the Blood-Brain Barrier
Langen, U. H., Ayloo, S., & Gu, C. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062608 · Cited by 533
“While Slc2a1−/− mice die at embryonic stages, mice haploinsufficient for Slc2a1 recapitulate the features seen in human patients (Wang et al. 2006).”
BackgroundNeurovascular and Cognitive Dysfunction in Hypertension
Iadecola, C., & Gottesman, R. F. (2019) · Circulation Research · doi:10.1161/circresaha.118.313260 · Cited by 530
“Recent single-cell RNA sequencing studies have started to unveil the molecular bases of the diversity of the cellular composition of the cerebrovascular tree.(52) These efforts, still in an initial stage, will provide critical insight into the cellular, molecular, and signaling mechanisms underlying the segmental susc…”
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Yang, A. C., Stevens, M. Y., Chen, M. B., Lee, D. P., Stähli, D., Gate, D., Contrepois, K., Chen, W., Iram, T., Zhang, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2453-z · Cited by 477
Mathys, H., Peng, Z., Boix, C. A., Victor, M. B., Leary, N., Babu, S., Abdelhady, G., Jiang, X., Ng, A. P., Ghafari, K., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.039 · Cited by 495
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Schupp, J. C., Adams, T. S., Cosme, C., Raredon, M. S. B., Yuan, Y., Omote, N., Poli, S., Chioccioli, M., Rose, K.-A., Manning, E. P., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.052318 · Cited by 453
What is a cell type and how to define it?
Zeng, H. (2022) · Cell · doi:10.1016/j.cell.2022.06.031 · Cited by 439
Yousef, H., Czupalla, C. J., Lee, D., Chen, M. B., Burke, A. N., Zera, K. A., Zandstra, J., Berber, E., Lehallier, B., Mathur, V., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0440-4 · Cited by 442
Parker, K. R., Migliorini, D., Perkey, E., Yost, K. E., Bhaduri, A., Bagga, P., Haris, M., Wilson, N. E., Liu, F., Gabunia, K., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.022 · Cited by 464
Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease
Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02263-w · Cited by 441
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Kaplan, L., Chow, B. W., & Gu, C. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0322-2 · Cited by 455
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Greene, C., Connolly, R., Brennan, D., Laffan, A., O’Keeffe, E., Zaporojan, L., O’Callaghan, J., Thomson, B., Connolly, E., Argue, R., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01576-9 · Cited by 429
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Nance, E. A., Pun, S. H., Saigal, R., & Sellers, D. L. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00394-w · Cited by 442
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He, L., Vanlandewijck, M., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Scientific Data · doi:10.1038/sdata.2018.160 · Cited by 413
Self-citationPericytes and Neurovascular Function in the Healthy and Diseased Brain
Brown, L. S., Foster, C. G., Courtney, J.-M., King, N. E., Howells, D. W., & Sutherland, B. A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00282 · Cited by 406
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Halpern, K. B., Shenhav, R., Massalha, H., Toth, B., Egozi, A., Massasa, E. E., Medgalia, C., David, E., Giladi, A., Moor, A. E., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4231 · Cited by 368
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Hartmann, D. A., Berthiaume, A., Grant, R. I., Harrill, S. A., Koski, T., Costello, J., Tieu, T., McDowell, K. P., Faino, A., Kelly, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00793-2 · Cited by 403
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Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression
Dudek, K. A., Dion-Albert, L., Lebel, M., LeClair, K., Labrecque, S., Tuck, E., Ferrer Perez, C., Golden, S. A., Tamminga, C., Turecki, G., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914655117 · Cited by 361
“Recent sequencing studies performed in whole mouse and human brains revealed that HDAC2 expression is higher than HDAC1 in endothelial cells (14, 40).”
A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution
Shapson-Coe, A., Januszewski, M., Berger, D. R., Pope, A., Wu, Y., Blakely, T., Schalek, R. L., Li, P. H., Wang, S., Maitin-Shepard, J., et al. (2024) · Science · doi:10.1126/science.adk4858 · Cited by 361
Genetic mapping of cell type specificity for complex traits
Watanabe, K., Mirkov, M. U., de Leeuw, C., van den Heuvel, M. P., & Posthuma, D. (2019) · Nature Communications · doi:10.1038/s41467-019-11181-1 · Cited by 329
Multisensory gamma stimulation promotes glymphatic clearance of amyloid
Murdock, M. H., Yang, C.-Y., Sun, N., Pao, P.-C., Blanco-Duque, C., Kahn, M. C., Kim, T., Lavoie, N. S., Victor, M. B., Islam, M. R., et al. (2024) · Nature · doi:10.1038/s41586-024-07132-6 · Cited by 379
“We further annotated vascular cells as endothelial cells, pericytes, smooth muscle cells and fibroblasts 28 (Fig.”
BackgroundSingle-cell multiregion dissection of Alzheimer’s disease
Mathys, H., Boix, C. A., Akay, L. A., Xia, Z., Davila-Velderrain, J., Ng, A. P., Jiang, X., Abdelhady, G., Galani, K., Mantero, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07606-7 · Cited by 343
“We annotated cell types using previously published marker genes and single-cell RNA-seq data 9,12,33,91–93 .”
A systems view of the vascular endothelium in health and disease
Augustin, H. G., & Koh, G. Y. (2024) · Cell · doi:10.1016/j.cell.2024.07.012 · Cited by 383
Kalluri, A. S., Vellarikkal, S. K., Edelman, E. R., Nguyễn, L., Subramanian, A., Ellinor, P. T., Regev, A., Kathiresan, S., & Gupta, R. M. (2019) · Circulation · doi:10.1161/circulationaha.118.038362 · Cited by 335
The anatomy and immunology of vasculature in the central nervous system
Mastorakos, P., & McGavern, D. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav0492 · Cited by 333
A single-cell atlas of the normal and malformed human brain vasculature
Winkler, E. A., Kim, C. N., Ross, J. M., Garcia, J. H., Gil, E., Oh, I., Chen, L. Q., Wu, D., Catapano, J. S., Raygor, K. P., et al. (2022) · Science · doi:10.1126/science.abi7377 · Cited by 324
Marchetti, L., & Engelhardt, B. (2020) · Vascular Biology · doi:10.1530/vb-19-0033 · Cited by 304
“Therefore we and others have extended referring to this vascular segment as BBB (9), as these characteristics impact on immune cell trafficking into the CNS (7, 10, 11).”
BackgroundSingle-cell dissection of the human brain vasculature
García, F., Sun, N., Lee, H., Godlewski, B. R., Mathys, H., Galani, K., Zhou, B., Jiang, X., Ng, A. P., Mantero, J. C., et al. (2022) · Nature · doi:10.1038/s41586-022-04521-7 · Cited by 313
Franjic, D., Skarica, M., Ma, S., Arellano, J. I., Tebbenkamp, A. T. N., Choi, J., Xu, C., Li, Q., Morozov, Y. M., Andrijevic, D., et al. (2022) · Neuron · doi:10.1016/j.neuron.2021.10.036 · Cited by 308
Single-Cell RNA Sequencing Maps Endothelial Metabolic Plasticity in Pathological Angiogenesis
Rohlenová, K., Goveia, J., García‐Caballero, M., Subramanian, A., Kalucka, J. M., Treps, L., Falkenberg, K. D., de Rooij, L. P. M. H., Zheng, Y., Lin, L., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.03.009 · Cited by 317
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306
“The mechanism underlying the difference is unclear but possibly related to the differential APOE receptor expression [295, 296], or isoform-specific impact on different vascular cell types [140, 297].”
BackgroundMicroglial metabolic flexibility supports immune surveillance of the brain parenchyma
Bernier, L., York, E. M., Kamyabi, A., Choi, H. B., Weilinger, N. L., & MacVicar, B. A. (2020) · Nature Communications · doi:10.1038/s41467-020-15267-z · Cited by 316
Single-cell RNA-seq reveals the transcriptional landscape in ischemic stroke
Zheng, K., Lin, L., Jiang, W., Chen, L., Zhang, X., Zhang, Q., Ren, Y., & Hao, J. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211026770 · Cited by 308
“We found six vascular endothelial cells (ECs) subclusters (Figure S10(a)) according to the established markers of ECs in previous studies.(44,45) Ischemia-induced inflammation and oxidative stress increased endothelial cell death, which directly resulted in the decrease of the cell percentage in the MCAO group, while,…”
BackgroundResultSpecification of CNS macrophage subsets occurs postnatally in defined niches
Masuda, T., Amann, L., Monaco, G., Sankowski, R., Staszewski, O., Krueger, M., Del Gaudio, F., He, L., Paterson, N., Nent, E., et al. (2022) · Nature · doi:10.1038/s41586-022-04596-2 · Cited by 294
Self-citationEndothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
Jambusaria, A., Hong, Z., Zhang, L., Srivastava, S., Jana, A., Tóth, P. T., Dai, Y., Malik, A. B., & Rehman, J. (2020) · eLife · doi:10.7554/elife.51413 · Cited by 299
Blanchard, J. W., Bula, M., Davila-Velderrain, J., Akay, L. A., Zhu, L., Frank, A., Victor, M. B., Bonner, J. M., Mathys, H., Lin, Y.-T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0886-4 · Cited by 283
Er, E. E., Valiente, M., Ganesh, K., Zou, Y., Agrawal, S., Hu, J., Griscom, B., Rosenblum, M., Boire, A., Brogi, E., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0138-8 · Cited by 292
Epigenetic Modifications in Cardiovascular Aging and Diseases
Zhang, W., Song, M., Qu, J. T., & Liu, G. (2018) · Circulation Research · doi:10.1161/circresaha.118.312497 · Cited by 296
“etic enzymes/pathways in specific diseased cohorts or cell types.(54,57,58,146) Altogether, new sequencing technologies have”
BackgroundImmunometabolism in the Brain: How Metabolism Shapes Microglial Function
Bernier, L., York, E. M., & MacVicar, B. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.08.008 · Cited by 308
Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord
Milich, L. M., Choi, J. S., Ryan, C. B., Cerqueira, S. R., Benavides, S., Yahn, S. L., Tsoulfas, P., & Lee, J. K. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20210040 · Cited by 289
A connectomic study of a petascale fragment of human cerebral cortex
Shapson-Coe, A., Januszewski, M., Berger, D. R., Pope, A., Wu, Y., Blakely, T., Schalek, R. L., Li, P. H., Wang, S., Maitin-Shepard, J., et al. (2021) · doi:10.1101/2021.05.29.446289 · Cited by 243
“Separation of smooth muscle cells from pericytes was possible in arteries and arterioles, however not clear in veins and venules as predicted by the expression profiles of these cells (Vanlandewijck et al. 2018).”
BackgroundDion‐Albert, L., Cadoret, A., Doney, E., Kaufmann, F. N., Dudek, K., Daigle, B., Parise, L. F., Cathomas, F., Samba, N., Hudson, N., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27604-x · Cited by 288
Shami, A. N., Zheng, X., Munyoki, S. K., Ma, Q., Manske, G. L., Green, C. D., Sukhwani, M., Orwig, K. E., Li, J. Z., & Hammoud, S. S. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.05.010 · Cited by 283
Hypertension, Neurovascular Dysfunction, and Cognitive Impairment
Santisteban, M. M., Iadecola, C., & Carnevale, D. (2022) · Hypertension · doi:10.1161/hypertensionaha.122.18085 · Cited by 317
Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development
Sur, A., Wang, Y., Capar, P., Margolin, G., Prochaska, M. K., & Farrell, J. A. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.11.001 · Cited by 280
Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells
Sabbagh, M. F., Heng, J. S., Luo, C., Castanon, R. G., Nery, J. R., Rattner, A., Goff, L. A., Ecker, J. R., & Nathans, J. (2018) · eLife · doi:10.7554/elife.36187 · Cited by 245
“A recent scRNA-seq study of adult mouse brain vasculature provided the first molecular profile of vascular zonation along the arteriovenous axis (Vanlandewijck et al., 2018).”
Brain endothelial GSDMD activation mediates inflammatory BBB breakdown
Wei, C., Jiang, W., Wang, R., Zhong, H., He, H., Gao, X., Zhong, S., Yu, F., Guo, Q., Zhang, L., et al. (2024) · Nature · doi:10.1038/s41586-024-07314-2 · Cited by 296
Molecular and anatomical organization of the dorsal raphe nucleus
Huang, K. W., Ochandarena, N. E., Philson, A. C., Hyun, M., Birnbaum, J. E., Cicconet, M., & Sabatini, B. L. (2019) · eLife · doi:10.7554/elife.46464 · Cited by 267
Molecular and cellular evolution of the primate dorsolateral prefrontal cortex
Ma, S., Škarica, M., Li, Q., Xu, C., Risgaard, R. D., Tebbenkamp, A. T. N., Mato-Blanco, X., Kovner, R., Krsnik, Ž., de Martin, X., et al. (2022) · Science · doi:10.1126/science.abo7257 · Cited by 257
“Through combinatorialmarker gene expression and transcriptomic integration withmouse snRNA-seq data (23, 24), we found that vascular subtypes were predicted to locate along the arterial-arteriolar-capillary-venous axis including three endothelial subtypes (arterial, capillary, andvenousendothelial cells), fourmural su…”
BackgroundDeSisto, J., O’Rourke, R., Jones, H. E., Pawlikowski, B., Malek, A. D., Bonney, S., Guimiot, F., Jones, K. L., & Siegenthaler, J. A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.009 · Cited by 241
“The lineage relationship between perivascular and meningeal fibroblasts has not been rigorously explored, though we and others have previously shown that collagen 1- expressing perivascular fibroblasts and meningeal fibroblasts express RALDH1, RALDH2, and PDGFRα (Vanlandewijck et al., 2018; Kelly et al., 2016).”
BackgroundPerivascular macrophages in health and disease
Lapenna, A., Palma, M. D., & Lewis, C. E. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0056-9 · Cited by 268
Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages
Mizrak, D., Levitin, H. M., Delgado, A. C., Crotet, V., Yuan, J., Chaker, Z., Silva-Vargas, V., Sims, P. A., & Doetsch, F. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.044 · Cited by 248
“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).”
Tmem119-EGFP and Tmem119-CreERT2 Transgenic Mice for Labeling and Manipulating Microglia
Kaiser, T., & Feng, G. (2019) · eneuro · doi:10.1523/eneuro.0448-18.2019 · Cited by 259
Markers for human brain pericytes and smooth muscle cells
Smyth, L. C. D., Rustenhoven, J., Scotter, E. L., Schweder, P. M., Faull, R. L. M., Park, T., & Dragunow, M. (2018) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2018.06.001 · Cited by 251
Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia
Rungta, R. L., Chaigneau, E. M., Osmanski, B.-F., & Charpak, S. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.012 · Cited by 245
Targeting pericytes for therapeutic approaches to neurological disorders
Cheng, J., Korte, N., Nortley, R., Sethi, H., Tang, Y., & Attwell, D. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1893-0 · Cited by 247
Herring, C. A., Simmons, R. K., Freytag, S., Poppe, D., Moffet, J. J. D., Pflueger, J., Buckberry, S., Vargas-Landín, D. B., Clément, O., Goñi, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.039 · Cited by 242
“, 2018), Endothelial cells: CLDN5 (Vanlandewijck et al., 2018), Fibroblast-like cells: TBX18 (Vanlandewijck et al.”
InfluentialBrain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues
Chen, M. B., Yang, A. C., Yousef, H., Lee, D., Chen, W., Schaum, N., Lehallier, B., Quake, S. R., & Wyss-Coray, T. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.012 · Cited by 233
“Vcam1, a cell surface receptor that facilities endothelialimmune cell interactions, has previously been shown to be highly enriched in arterial and venous cells (Vanlandewijck et al., 2018; Yousef et al., 2019).”
InfluentialIdentification, discrimination and heterogeneity of fibroblasts
Lendahl, U., Muhl, L., & Betsholtz, C. (2022) · Nature Communications · doi:10.1038/s41467-022-30633-9 · Cited by 256
Self-citationBrain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia
Uemura, M. T., Maki, T., Ihara, M., Lee, V. M. ‐., & Trojanowski, J. Q. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00080 · Cited by 246
Caveolae in CNS arterioles mediate neurovascular coupling
Chow, B. W., Nuñez, V., Kaplan, L., Granger, A. J., Bistrong, K., Zucker, H. L., Kumar, P., Sabatini, B. L., & Gu, C. (2020) · Nature · doi:10.1038/s41586-020-2026-1 · Cited by 244
Advances in Understanding the Pathophysiology of Lacunar Stroke
Regenhardt, R. W., Das, A. S., Lo, E. H., & Caplan, L. R. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.1073 · Cited by 237
Cognitive impact of COVID-19: looking beyond the short term
Miners, J. S., Kehoe, P. G., & Love, S. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00744-w · Cited by 261
Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential
Huang, S., Ziegler, C. G. K., Austin, J., Mannoun, N., Vukovic, M., Ordovás-Montañés, J., Shalek, A. K., & von Andrian, U. H. (2020) · Cell · doi:10.1016/j.cell.2020.11.028 · Cited by 234
“The second blood endothelial cell cluster, termed BEC, includes a heterogeneous set of non-HEV endothelial cells, including arterial, capillary, and non-HEV venular cells (Figures S5H and S5I; Vanlandewijck et al., 2018).”
BackgroundGreene, C., Hanley, N., & Campbell, M. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01054-3 · Cited by 221
Contractile pericytes determine the direction of blood flow at capillary junctions
Gonzales, A. L., Klug, N. R., Moshkforoush, A., Lee, J. C., Lee, F. K., Shui, B., Tsoukias, N. M., Kotlikoff, M. I., Hill‐Eubanks, D. C., & Nelson, M. T. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922755117 · Cited by 220
“Curiously, although these cells express tubulin monomers (26, 27), they lacked polymerized tubulin (i.”
BackgroundCellular architecture of human brain metastases
Velozo, H. G., Mei, W., Robles, I., Hagerling, C., Allen, B. M., Okholm, T. L. H., Nanjaraj, A., Verbeek, T. C. A. I., Kalavacherla, S., van Gogh, M., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.043 · Cited by 224
Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants
Persyn, E., Hanscombe, K. B., Howson, J. M. M., Lewis, C. M., Traylor, M., & Markus, H. S. (2020) · Nature Communications · doi:10.1038/s41467-020-15932-3 · Cited by 208
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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