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.
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In the citing paper
“many of which were well documented61–66.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [64]
In the citing paper
“We identified endothelial ICs (Figure 2E) with strong contributions from genes with arterial (IC 5 and 20) and veinous (IC 3 and 12) expression, suggesting heterogeneity related to vessel type”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“These genes (e.g. Tm4sf1 and Slc38a5) showed continuous, reciprocal expression (Data S4G), consistent with the smooth molecular transitions described for endothelial cells associated with arteries or veins”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“IC 19 represented this difference in a graded rather than categorical way, as Rgs5/Acta2 expression and IC cell scores were continuously, rather than bimodally, distributed across these cells”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Among SMA cells, Acta2 expression correlates with a veinous versus arterial distribution”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“A single IC (IC 13) appeared to encode this distinction, with pericyte marker Vtn as the strongest loading gene”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Like Vanlandewijck et al., we observed (Figure 5) distinct endothelial cell types carrying known arterial (e.g., Bmx; VECA) and venous (Slc38a5; VECV) markers, as well as capillary endothelial cells (VECC) expressing Meox1.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Vanlandewijck et al. described two brain fibroblast-like cell types expressing fibril-forming collagens (e.g., Col1a1, Col1a2), collagen fiber crosslinking proteins (Lum, Dcn), and the platelet-derived growth factor receptor alpha, Pdgfra, which was interposed between astrocyte endfeet and vascular endothelial cells.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“In vivo, αSMA and calponin expression are restricted to mural cells along brain arterioles and arteries [38], however, these markers are often upregulated during culture [39], complicating identification of pericytes.”
From Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D (2019) · cites this paper as [38]
In the citing paper
“APOE in the brain is primarily synthesized by astrocytes and microglia, as indicated by a recent single cell RNA-seq study in the mouse (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Pericytes, SMCs, and endothelial cells express thousands of transcripts encoding different transporters, receptors, active efflux pumps, ion channels, and regulatory molecules (28, 72, 86, 129, 242, 358, 359, 610, 675, 678), whose expression pattern varies by zonation along the arteriocapillary-venous axis and cell type (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“In contrast to the BBB endothelium's gradual phenotypic change along the arteriovenous axis, mural cells formed two distinct groups comprising pericyte and venous SMCs, and arterial and arteriole SMCs (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Briefly, this study is the first to report that at the BBB endothelium transcription factors predominated at arteries and arterioles, transporters predominated capillaries and veins, and ribosomal proteins indicative of protein synthesis were spread along the arteriovenous axis (610), yielding important insights to biological functions and endothelial specialization along the brain vasculature”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“According to a transcriptomic analysis of cells in the vasculature, Plcg2 seems to be expressed in certain subtypes of endothelial cells, although at lower level than compared to microglia (http://betsholtzlab.org/VascularSingleCells/database.html [43]).”
From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [43]
In the citing paper
“we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types [27].”
From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [27]
In the citing paper
“Here, we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types.34”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [34]
In the citing paper
“WAVE2 is expressed at high levels in microglia and vascular endothelial cells14,15.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [14]
In the citing paper
“In addition to astrocytes and microglia, other cell types in the brain have been reported to produce ApoE under different conditions. These cells include oligodendrocytes, pericytes, vascular smooth muscle cells, perivascular fibroblasts, and perivascular macrophages [107–109].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [108]
In the citing paper
“PDGFRβ expression in pericytes is noticeably higher than in SMCs18,25,26.”
From Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction (2019) · cites this paper as [25]
In the citing paper
“Based on marker gene enrichment (Table S1), Endo.1 may correspond to endothelial capillary cells, Endo.2 to venous endothelial cells, and Endo.3 to arterial endothelial cells (Vanlandewijck et al., 2018).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“We spatially mapped the developing arterio-venous zonation in the embryonic LV ChP in whole explants by combining the pan-endothelial marker PECAM1 with markers for arteries (Acta2+, Vwf+) and veins (Acta2−, Vwf+) (Vanlandewijck et al., 2018).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Vanlandewijck et al., 2018
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Cited by
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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
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Molecular diversity and specializations among the cells of the adult mouse brain
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BackgroundResultInfluentialBlood–brain barrier breakdown is an early biomarker of human cognitive dysfunction
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The blood–brain barrier and blood–tumour barrier in brain tumours and metastases
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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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