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A molecular atlas of cell types and zonation in the brain vasculature
Open accessAbstract
Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.
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In the citing paper
“many of which were well documented61–66.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [64]
In the citing paper
“We identified endothelial ICs (Figure 2E) with strong contributions from genes with arterial (IC 5 and 20) and veinous (IC 3 and 12) expression, suggesting heterogeneity related to vessel type”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“These genes (e.g. Tm4sf1 and Slc38a5) showed continuous, reciprocal expression (Data S4G), consistent with the smooth molecular transitions described for endothelial cells associated with arteries or veins”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“IC 19 represented this difference in a graded rather than categorical way, as Rgs5/Acta2 expression and IC cell scores were continuously, rather than bimodally, distributed across these cells”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Among SMA cells, Acta2 expression correlates with a veinous versus arterial distribution”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“A single IC (IC 13) appeared to encode this distinction, with pericyte marker Vtn as the strongest loading gene”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Like Vanlandewijck et al., we observed (Figure 5) distinct endothelial cell types carrying known arterial (e.g., Bmx; VECA) and venous (Slc38a5; VECV) markers, as well as capillary endothelial cells (VECC) expressing Meox1.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Vanlandewijck et al. described two brain fibroblast-like cell types expressing fibril-forming collagens (e.g., Col1a1, Col1a2), collagen fiber crosslinking proteins (Lum, Dcn), and the platelet-derived growth factor receptor alpha, Pdgfra, which was interposed between astrocyte endfeet and vascular endothelial cells.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“In vivo, αSMA and calponin expression are restricted to mural cells along brain arterioles and arteries [38], however, these markers are often upregulated during culture [39], complicating identification of pericytes.”
From Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D (2019) · cites this paper as [38]
In the citing paper
“APOE in the brain is primarily synthesized by astrocytes and microglia, as indicated by a recent single cell RNA-seq study in the mouse (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Pericytes, SMCs, and endothelial cells express thousands of transcripts encoding different transporters, receptors, active efflux pumps, ion channels, and regulatory molecules (28, 72, 86, 129, 242, 358, 359, 610, 675, 678), whose expression pattern varies by zonation along the arteriocapillary-venous axis and cell type (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“In contrast to the BBB endothelium's gradual phenotypic change along the arteriovenous axis, mural cells formed two distinct groups comprising pericyte and venous SMCs, and arterial and arteriole SMCs (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Briefly, this study is the first to report that at the BBB endothelium transcription factors predominated at arteries and arterioles, transporters predominated capillaries and veins, and ribosomal proteins indicative of protein synthesis were spread along the arteriovenous axis (610), yielding important insights to biological functions and endothelial specialization along the brain vasculature”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“According to a transcriptomic analysis of cells in the vasculature, Plcg2 seems to be expressed in certain subtypes of endothelial cells, although at lower level than compared to microglia (http://betsholtzlab.org/VascularSingleCells/database.html [43]).”
From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [43]
In the citing paper
“we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types [27].”
From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [27]
In the citing paper
“Here, we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types.34”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [34]
In the citing paper
“WAVE2 is expressed at high levels in microglia and vascular endothelial cells14,15.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [14]
In the citing paper
“In addition to astrocytes and microglia, other cell types in the brain have been reported to produce ApoE under different conditions. These cells include oligodendrocytes, pericytes, vascular smooth muscle cells, perivascular fibroblasts, and perivascular macrophages [107–109].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [108]
In the citing paper
“PDGFRβ expression in pericytes is noticeably higher than in SMCs18,25,26.”
From Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction (2019) · cites this paper as [25]
In the citing paper
“Based on marker gene enrichment (Table S1), Endo.1 may correspond to endothelial capillary cells, Endo.2 to venous endothelial cells, and Endo.3 to arterial endothelial cells (Vanlandewijck et al., 2018).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“We spatially mapped the developing arterio-venous zonation in the embryonic LV ChP in whole explants by combining the pan-endothelial marker PECAM1 with markers for arteries (Acta2+, Vwf+) and veins (Acta2−, Vwf+) (Vanlandewijck et al., 2018).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Vanlandewijck et al., 2018
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ResultCardiac Remodeling in Chronic Kidney Disease
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“The heterogeneity of perivascular cells has been unclear for many years, but recent single-cell RNA-sequencing data suggest that various, previously unknown, perivascular mesenchymal populations exist [28,29].”
BackgroundInsights into Alzheimer’s disease from single-cell genomic approaches
Murdock, M. H., & Tsai, L.-H. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01222-2 · Cited by 148
Wan, X., Xiao, J., Tam, S. S. T., Cai, M., Sugimura, R., Wang, Y., Wan, X., Lin, Z., Wu, A. R., & Yang, C. (2023) · Nature Communications · doi:10.1038/s41467-023-43629-w · Cited by 166
Benchmarking in vitro tissue-engineered blood–brain barrier models
DeStefano, J. G., Jamieson, J. J., Linville, R. M., & Searson, P. C. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0117-2 · Cited by 142
PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells
Harraz, O. F., Longden, T. A., Hill-Eubanks, D., & Nelson, M. T. (2018) · eLife · doi:10.7554/elife.38689 · Cited by 149
“Along these lines, a recent single-cell transcriptomics analysis showed that Gaq (Gnaq) transcript levels in the mouse brain endothelium are reduced compared with those in peripheral pulmonary ECs (Vanlandewijck et al., 2018).”
BackgroundA Single-Cell Transcriptional Roadmap of the Mouse and Human Lymph Node Lymphatic Vasculature
Xiang, M., Grosso, R. A., Takeda, A., Pan, J., Bekkhus, T., Brulois, K., Đermadi, D., Nordling, S., Vanlandewijck, M., Jalkanen, S., et al. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00052 · Cited by 143
Self-citationAstrocyte-derived Wnt growth factors are required for endothelial blood-brain barrier maintenance
Guérit, S., Fidan, E., Macas, J., Czupalla, C. J., de Figueiredo, R. M., Vijikumar, A., Yalcin, B. H., Thom, S., Winter, P., Gerhardt, H., et al. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101937 · Cited by 155
“…as recently shown by Vanlandewijck as well as by Zhang and colleagues, pericytes do not express Wnt7a/Wnt7b whereas ACs appear to be the CNS cell type predominantly expressing these barrier-relevant growth factors in the adult mouse brain (Vanlandewijck et al., 2018; Zhang et al., 2014).”
BackgroundMethodInfluentialEvaluating measures of association for single-cell transcriptomics
Skinnider, M. A., Squair, J. W., & Foster, L. J. (2019) · Nature Methods · doi:10.1038/s41592-019-0372-4 · Cited by 145
Blood–brain barrier alterations and their impact on Parkinson’s disease pathogenesis and therapy
Lau, K., Kotzur, R., & Richter, F. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00430-z · Cited by 174
“A molecular atlas of the human brain vasculature has been constructed [190], and it further provides the possibility to identify pathologic transformation of cells and of the vascular pattern in diseased brains [191].”
BackgroundMethodAlzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph
Magno, L., Lessard, C. B., Martins, M., Lang, V., Cruz, P., Asi, Y., Katan, M., Bilsland, J., Lashley, T., Chakrabarty, P., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0469-0 · Cited by 143
PDGF-B Is Required for Development of the Glymphatic System
Munk, A. S. F., Wang, W., Bèchet, N. B., Eltanahy, A. M., Cheng, A. X., Sigurðsson, B., Benraiss, A., Mäe, M. A., Kress, B. T., Kelley, D. H., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.050 · Cited by 147
“Pericytes express laminin α2 and agrin (Vanlandewijck et al., 2018), both of which bind to α-dystroglycan, which connects to α-syntrophin and dystrophin as part of an anchoring complex (dystrophin-associated protein complex [DAPC]) for AQP4 in the astrocyte endfeet (Neely et al., 2001; Wolburg et…”
BackgroundInfluentialSelf-citationEmerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes
Lendahl, U., Nilsson, P., & Betsholtz, C. (2019) · EMBO Reports · doi:10.15252/embr.201948070 · Cited by 148
“The latter is suggested by the many transporter molecules that are specifically expressed in brain pericytes as compared to lung pericytes [17].”
InfluentialSelf-citationRedefining the heterogeneity of peripheral nerve cells in health and autoimmunity
Wolbert, J., Li, X., Heming, M., Mausberg, A. K., Akkermann, D., Frydrychowicz, C., Fledrich, R., Groeneweg, L., Schulz, C., Stettner, M., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1912139117 · Cited by 140
“Vascular clusters expressed canonical markers of vascular smooth muscle cells (vSMCs; Acta2, Tagln, and Tpm2), of pericytes (PCs; Rgs5 and Pdgrfb), of lymphatic endothelial cells (lymph; Lyve1 and Prox1), and of vascular endothelial cells (EC1s; Cldn5, Egfl7, and Pecam1) (10) (Fig.”
BackgroundInfluentialMolecular anatomy of adult mouse leptomeninges
Pietilä, R., Del Gaudio, F., He, L., Vázquez-Liébanas, E., Vanlandewijck, M., Muhl, L., Mocci, G., Bjørnholm, K. D., Lindblad, C., Fletcher-Sandersjöö, A., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.09.002 · Cited by 145
“28 To determine the spatial relationship of BFB2 and BFB3, we performed co-ISH for Sidt1 (a marker of BFB2 and neurons) and Ppp1r1a (BFB3).”
InfluentialSelf-citationPrecision drug delivery to the central nervous system using engineered nanoparticles
Gao, J., Xia, Z. J., Gunasekar, S., Jiang, C., Karp, J. M., & Joshi, N. (2024) · Nature Reviews Materials · doi:10.1038/s41578-024-00695-w · Cited by 173
Integrated multi-omic characterization of congenital heart disease
Hill, M. C., Kadow, Z. A., Long, H., Morikawa, Y., Martin, T. J., Birks, E. J., Campbell, K. S., Nerbonne, J. M., Lavine, K. J., Wadhwa, L., et al. (2022) · Nature · doi:10.1038/s41586-022-04989-3 · Cited by 150
Current and emerging avenues for Alzheimer's disease drug targets
Loera‐Valencia, R., Cedazo-Mínguez, Á., Kenigsberg, P.-A., Page, G., Duarte, A. I., Giusti, P., Zusso, M., Robert, P. H., Frisoni, G. B., Cattaneo, A., et al. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12959 · Cited by 142
Rodor, J., Chen, S.-H., Scanlon, J. P., Monteiro, J. P., Caudrillier, A., Sweta, S., Stewart, K. R., Shmakova, A., Dobie, R., Henderson, B. E. P., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab296 · Cited by 138
“We analysed zonation-dependent changes across the arteriovenous axis in PAH, confirming the continuum of transcriptional states, as previously described for brain ECs.(19) The comparison between PAH and Control samples revealed specific gene regulation in distinct regions of the axis.”
InfluentialKumar, P., Lim, A., Hazirah, S. N., Chua, C. J. H., Ngoh, A., Poh, S. L., Yeo, T. H., Lim, J., Ling, S., Sutamam, N. B., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01095-5 · Cited by 142
Han, B., Zhou, S., Zhang, Y., Chen, S., Xi, W., Liu, C., Zhou, X., Yuan, M., Yu, X., Li, L., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adg1323 · Cited by 143
GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism
Young, S. G., Fong, L. G., Beigneux, A. P., Allan, C. M., He, C. H., Jiang, H., Nakajima, K., Muthuraman, M., Birrane, G., & Ploug, M. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.023 · Cited by 148
“Consistent with immunohistochemistry studies, Gpihbp1 transcripts are absent from capillary endothelial cells of the brain, as judged by single-cell RNA-seq studies (He et al., 2018b; Vanlandewijck et al., 2018).”
BackgroundCardiac cell type–specific gene regulatory programs and disease risk association
Hocker, J. D., Poirion, O., Zhu, F., Buchanan, J., Zhang, K., Chiou, J., Wang, T., Zhang, Q., Hou, X., Li, Y. E., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf1444 · Cited by 136
Endothelial S1P 1 Signaling Counteracts Infarct Expansion in Ischemic Stroke
Nitzsche, A., Poittevin, M., Benarab, A., Bonnin, P., Faraco, G., Uchida, H., Favre, J., García‐Bonilla, L., Garcia, M. C., Léger, P., et al. (2020) · Circulation Research · doi:10.1161/circresaha.120.316711 · Cited by 140
Reverse-translational identification of a cerebellar satiation network
Low, A. Y. T., Goldstein, N., Gaunt, J. R., Huang, K.-P., Zainolabidin, N., Yip, A. K. K., Carty, J. R. E., Choi, J. Y., Miller, A. M., Ho, H. S. T., et al. (2021) · Nature · doi:10.1038/s41586-021-04143-5 · Cited by 135
Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain
Crouch, E. E., Bhaduri, A., Andrews, M. G., Cebrián‐Silla, A., Diafos, L. N., Birrueta, J. O., Wedderburn-Pugh, K., Valenzuela, E. J., Bennett, N. K., Eze, U. C., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.004 · Cited by 139
Vascular and neural basis of the BOLD signal
Drew, P. J. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.06.004 · Cited by 165
“There is a robust arterial–venous gradient in gene expression patterns [28] and in smooth muscle/pericyte coverage”
Neurovascular Interactions in the Nervous System
Segarra, M., Aburto, M. R., Hefendehl, J. K., & Acker‐Palmer, A. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125142 · Cited by 137
Endothelial Unc5B controls blood-brain barrier integrity
Boyé, K., Geraldo, L. H., Furtado, J., Pibouin-Fragner, L., Poulet, M., Kim, D., Nelson, B., Xu, Y., Jacob, L., Maïssa, N., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28785-9 · Cited by 144
“Since Netrin-1 mRNA is produced by several cell types in the adult brain 49 , we generated temporally inducible Netrin-1 global KO mice by crossing Ntn1 fl / fl mice 50 with RosaCre ERT2 mice (hereafter Ntn1iko ), to induce ubiquitous gene deletion upon TAM injection.”
Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain
Dai, J., Cimino, P. J., Gouin, K. H., Grzelak, C. A., Barrett, A. S., Lim, A. R., Long, A., Weaver, S., Saldin, L. T., Uzamere, A., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00297-3 · Cited by 138
Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin
Duong, C. N., & Vestweber, D. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00519 · Cited by 134
Sun, J., Huang, Y., Gong, J., Wang, J., Fan, Y., Cai, J., Wang, Y., Qiu, Y., Wei, Y., Xiong, C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19042-y · Cited by 132
Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer’s disease
Zhu, W. M., Neuhaus, A. A., Beard, D. J., Sutherland, B. A., & DeLuca, G. C. (2022) · Brain · doi:10.1093/brain/awac174 · Cited by 144
“osin expression but absent or very low expression of Acta2 (αSMA).(74) Nevertheless, a recent study has shown that following optogenetic stimulation, pericytes exert a slow vasoconstriction that slows red blood cell flux.”
BackgroundLiving on the Edge of the CNS: Meninges Cell Diversity in Health and Disease
Derk, J., Jones, H. E., Como, C., Pawlikowski, B., & Siegenthaler, J. A. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703944 · Cited by 120
Tight junction modulation at the blood-brain barrier: Current and future perspectives
Hashimoto, Y., & Campbell, M. (2020) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2020.183298 · Cited by 138
Korte, N., Ilkan, Z., Pearson, C. L., Pfeiffer, T., Singhal, P., Rock, J., Sethi, H., Gill, D., Attwell, D., & Tammaro, P. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154118 · Cited by 135
“The Nobel Prize was awarded to Krogh in 1920 for his discovery of contractile elements (now termed peri-cytes) on capillaries, which act independently of SMCs on arterioles (70).”
Recent advances in human iPSC-derived models of the blood–brain barrier
Workman, M. J., & Svendsen, C. N. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00191-7 · Cited by 136
Genome-wide spatial expression profiling in formalin-fixed tissues
Gracia Villacampa, E., Larsson, L., Mirzazadeh, R., Kvastad, L., Andersson, A., Mollbrink, A., Kokaraki, G., Monteil, V., Schultz, N., Appelberg, K. S., et al. (2021) · Cell Genomics · doi:10.1016/j.xgen.2021.100065 · Cited by 132
Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles
Thomsen, M. S., Johnsen, K. B., Kucharz, K., Lauritzen, M., & Moos, T. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14102237 · Cited by 135
Molecular determinants of nephron vascular specialization in the kidney
Barry, D. M., McMillan, E. A., Kunar, B., Lis, R., Zhang, T., Lu, T. M., Daniel, E., Yokoyama, M., Gómez-Salinero, J. M., Sureshbabu, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12872-5 · Cited by 130
Endothelial LRP1 protects against neurodegeneration by blocking cyclophilin A
Nikolakopoulou, A. M., Wang, Y., Ma, Q., Sagare, A. P., Montagne, A., Huuskonen, M. T., Rege, S. V., Kisler, K., Dai, Z., Körbelin, J., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202207 · Cited by 131
Vascular endothelial cell specification in health and disease
Marziano, C., Genet, G., & Hirschi, K. K. (2021) · Angiogenesis · doi:10.1007/s10456-021-09785-7 · Cited by 136
“Due, in part, to this venous to artery migration, brain capillary ECs share gene expression patterns of both venous and arterial ECs [76].”
BackgroundBrain endothelial cell TRPA1 channels initiate neurovascular coupling
Thakore, P., Alvarado, M. G., Ali, S., Mughal, A., Pires, P. W., Yamasaki, E., Pritchard, H. A. T., Isakson, B. E., Tran, C. H. T., & Earley, S. (2021) · eLife · doi:10.7554/elife.63040 · Cited by 128
“Released ATP subsequently activates Ca-permeable ionotropic purinergic (P2X) receptors on adjacent cells to increase intracellular Ca , providing a means for the intercellular propagation of Ca signals (Barbe et al., 2006; Locovei et al., 2006; Suadicani et al., 2009; Vanlandewijck et al., 2018; Zsembery et al., 2003).”
BackgroundThe CLDN5 gene at the blood-brain barrier in health and disease
Hashimoto, Y., Greene, C., Münnich, A., & Campbell, M. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00424-5 · Cited by 136
“CLDN-5 expression is highly regulated by endothelial specific transcriptional regulators (Table 1), but CLDN12 and -25 are not; these CLDNs are expressed in many tissues and cell types with low to intermediate expression level except for CLDN-25 in oligodendrocytes [9].”
BackgroundResultInfluentialGonzalez-Carter, D., Liu, X., Tockary, T. A., Dirisala, A., Toh, K., Anraku, Y., & Kataoka, K. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002016117 · Cited by 127
“While PECAM-1 is known to be expressed by venous, capillary, and arterial ECs in the brain microvasculature (20), such relatively limited interendothelial distribution would allow for only a fraction of the cell surface to display targets, thereby not achieving maximal nanoparticle uptake.”
BackgroundA molecular map of murine lymph node blood vascular endothelium at single cell resolution
Brulois, K., Rajaraman, A., Szade, A., Nordling, S., Bogoslowski, A., Đermadi, D., Rahman, M., Kiefel, H., O’Hara, E., Koning, J. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17291-5 · Cited by 125
Gui, Y., Marks, J. D., Das, S., Hyman, B. T., & Serrano‐Pozo, A. (2020) · Brain Pathology · doi:10.1111/bpa.12763 · Cited by 126
“Analysis of publicly available RNA-Seq datasets The cell types expressing tspo mRNA were ascertained in the mouse and human RNA-Seq datasets made publicly available by the Barres (1, 53, 54) and Betsholtz (2, 16, 48) labs.”
MethodA Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury
Zamboni, M., Llorens-Bobadilla, E., Magnusson, J. P., & Frisén, J. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.07.006 · Cited by 131
Zhao, L., Li, Z., Vong, J. S. L., Chen, X., Lai, H. M., Yan, L. Y. C., Huang, J., Sy, S. K. H., Tian, X. Y., Huang, Y., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18249-3 · Cited by 125
Tan, C., Lu, N., Wang, C., Chen, D.-Y., Sun, N.-H., Lyu, H., Körbelin, J., Shi, W., Fukunaga, K., Lu, Y., et al. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.036 · Cited by 128
Berthier, A., Johanns, M., Zummo, F. P., Lefebvre, P., & Staels, B. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166097 · Cited by 125
“Interestingly, while it has been mainly characterized in the liver, new data suggest that zonation may also occur in other organs like the kidney [68], intestine [69] and brain [70].”
BackgroundCauses and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease
Bracko, O., Hernández, J. C. C., Park, L., Nishimura, N., & Schaffer, C. B. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20982383 · Cited by 127
“This zonation of the cerebral vasculature was recently described in detail.(15) These differences in topology and cellular structure along the vasculature reflects varying functional roles of different vessel classes.”
BackgroundSingle-cell transcriptomics for the assessment of cardiac disease
Miranda, A. M. A., Janbandhu, V., Maatz, H., Kanemaru, K., Cranley, J., Teichmann, S. A., Hübner, N., Schneider, M. D., Harvey, R. P., & Noseda, M. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00805-7 · Cited by 117
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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