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A molecular atlas of cell types and zonation in the brain vasculature
Open accessAbstract
Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.
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“many of which were well documented61–66.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [64]
In the citing paper
“We identified endothelial ICs (Figure 2E) with strong contributions from genes with arterial (IC 5 and 20) and veinous (IC 3 and 12) expression, suggesting heterogeneity related to vessel type”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“These genes (e.g. Tm4sf1 and Slc38a5) showed continuous, reciprocal expression (Data S4G), consistent with the smooth molecular transitions described for endothelial cells associated with arteries or veins”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“IC 19 represented this difference in a graded rather than categorical way, as Rgs5/Acta2 expression and IC cell scores were continuously, rather than bimodally, distributed across these cells”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Among SMA cells, Acta2 expression correlates with a veinous versus arterial distribution”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“A single IC (IC 13) appeared to encode this distinction, with pericyte marker Vtn as the strongest loading gene”
From Molecular diversity and specializations among the cells of the adult mouse brain (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Like Vanlandewijck et al., we observed (Figure 5) distinct endothelial cell types carrying known arterial (e.g., Bmx; VECA) and venous (Slc38a5; VECV) markers, as well as capillary endothelial cells (VECC) expressing Meox1.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“Vanlandewijck et al. described two brain fibroblast-like cell types expressing fibril-forming collagens (e.g., Col1a1, Col1a2), collagen fiber crosslinking proteins (Lum, Dcn), and the platelet-derived growth factor receptor alpha, Pdgfra, which was interposed between astrocyte endfeet and vascular endothelial cells.”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“In vivo, αSMA and calponin expression are restricted to mural cells along brain arterioles and arteries [38], however, these markers are often upregulated during culture [39], complicating identification of pericytes.”
From Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D (2019) · cites this paper as [38]
In the citing paper
“APOE in the brain is primarily synthesized by astrocytes and microglia, as indicated by a recent single cell RNA-seq study in the mouse (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Pericytes, SMCs, and endothelial cells express thousands of transcripts encoding different transporters, receptors, active efflux pumps, ion channels, and regulatory molecules (28, 72, 86, 129, 242, 358, 359, 610, 675, 678), whose expression pattern varies by zonation along the arteriocapillary-venous axis and cell type (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“In contrast to the BBB endothelium's gradual phenotypic change along the arteriovenous axis, mural cells formed two distinct groups comprising pericyte and venous SMCs, and arterial and arteriole SMCs (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“Briefly, this study is the first to report that at the BBB endothelium transcription factors predominated at arteries and arterioles, transporters predominated capillaries and veins, and ribosomal proteins indicative of protein synthesis were spread along the arteriovenous axis (610), yielding important insights to biological functions and endothelial specialization along the brain vasculature”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [610]
In the citing paper
“According to a transcriptomic analysis of cells in the vasculature, Plcg2 seems to be expressed in certain subtypes of endothelial cells, although at lower level than compared to microglia (http://betsholtzlab.org/VascularSingleCells/database.html [43]).”
From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [43]
In the citing paper
“we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types [27].”
From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [27]
In the citing paper
“Here, we used an siRNA sequence targeting Ppib because this gene is abundantly and ubiquitously expressed across CNS cell types.34”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [34]
In the citing paper
“WAVE2 is expressed at high levels in microglia and vascular endothelial cells14,15.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [14]
In the citing paper
“In addition to astrocytes and microglia, other cell types in the brain have been reported to produce ApoE under different conditions. These cells include oligodendrocytes, pericytes, vascular smooth muscle cells, perivascular fibroblasts, and perivascular macrophages [107–109].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [108]
In the citing paper
“PDGFRβ expression in pericytes is noticeably higher than in SMCs18,25,26.”
From Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction (2019) · cites this paper as [25]
In the citing paper
“Based on marker gene enrichment (Table S1), Endo.1 may correspond to endothelial capillary cells, Endo.2 to venous endothelial cells, and Endo.3 to arterial endothelial cells (Vanlandewijck et al., 2018).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Vanlandewijck et al., 2018
In the citing paper
“We spatially mapped the developing arterio-venous zonation in the embryonic LV ChP in whole explants by combining the pan-endothelial marker PECAM1 with markers for arteries (Acta2+, Vwf+) and veins (Acta2−, Vwf+) (Vanlandewijck et al., 2018).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Vanlandewijck et al., 2018
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Myc‐dependent endothelial proliferation is controlled by phosphotyrosine 1212 in VEGF receptor‐2
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“Arterial nuclei represented 20% ± 8.2 of the midbrain endothelial cells (S. Table 11) and highly expressed previously reported arterial markers, such as VEGFC, EFNB2, and FBLN5 [65, 66], and novel markers, such as IGFBP3, DKK2, and ROR1 (Fig.”
BackgroundInfluentialTranscription factors regulating vasculogenesis and angiogenesis
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“102,105,106 Of these adult ETS, all but Elk1 are also expressed in angioblasts in E8.”
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“According to the Betsholtz mouse database, the expression of ACE2 is very high in microvascular mural cells (such as pericytes and venous vascular smooth muscle cells), but not in endothelial cells [35, 62, 84].”
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“Moreover, although brain ECs have been analyzed at the single-cell level, 8,13,18 how brain EC selectively enriched transcripts and proteins are expressed along the vascular tree remains unclear.”
BackgroundResultLong-range inhibitory neurons mediate cortical neurovascular coupling
Ruff, C. F., Anaya, F. J., Dienel, S. J., Rakymzhan, A., Altamirano-Espinoza, A., Couey, J. J., Fukuda, M., Watson, A. M., Su, A., Fish, K. N., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113970 · Cited by 36
“27,28 However, other studies have concluded that a type of pericytes, ensheathing pericytes, are contractile and control CBF through the regulation of capillary diameter.”
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Synergistic induction of blood–brain barrier properties
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Dynamic modulation of the blood–brain barrier in the healthy brain
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Photobiomodulation drives pericyte mobilization towards skin regeneration
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“Stebbins et al. (2019) using a medium with added fetal bovine serum showed that NCSCs were induced into pericytes expressing NG2, PDGFRβ, and αSMAlow (Gastfriend et al., 2021).”
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“Both occludin and JAM2 are mainly expressed in endothelial cells in the CNS.(5) The contribution of JAM2 to the integrity of the tight junction in the BBB may be minor(29) but occludin is known to enhance the complexity of tight junction strands and the knockdown of occludin attenuated TEER of a brain endothelial cell…”
BackgroundMechanisms of cerebrospinal fluid and brain interstitial fluid production
Xiang, J., Hua, Y., Xi, G., & Keep, R. F. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106159 · Cited by 37
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InfluentialProtective fibroblastic niches in secondary lymphoid organs
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Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19
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“111,112 Hence, at the capillary level extracellular increases in K + concentration may initiate the start of the propagated vasodilatory response, with eNOS regulating up-stream to increase precision of spatiotemporal CBF distribution, either through neuronal glutaminergic signalling or glial ATP…”
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Brain endothelial specific gene therapy improves experimental Sandhoff disease
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Transcription factor FOXP2 is a flow‐induced regulator of collecting lymphatic vessels
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Self-citationSingle-cell transcriptomic landscape of cardiac neural crest cell derivatives during development
Chen, W., Liu, X., Li, W., Shen, H., Zeng, Z., Yin, K., Priest, J. R., & Zhou, Z. (2021) · EMBO Reports · doi:10.15252/embr.202152389 · Cited by 33
“The large-scale single-cell RNA-seq dataset gave us an unpreceded opportunity since the cells were clustered in an unbiased manner based on the whole transcriptome, without the need for a priori knowledge about the cell markers.”
InfluentialPerivascular stromal cells: Directors of tissue immune niches
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“Our Western blot results are consistent with the studies that have previously indicated that lung endothelium expresses tau (28, 29).”
ResultNeuronal activity drives IGF2 expression from pericytes to form long-term memory
Pandey, K. R., Bessières, B., Sheng, S. L., Taranda, J., Osten, P., Sandovici, I., Constância, M., & Alberini, C. M. (2023) · Neuron · doi:10.1016/j.neuron.2023.08.030 · Cited by 34
Specialized Retinal Endothelial Cells Modulate Blood-Retina Barrier in Diabetic Retinopathy
Yao, X., Zhao, Z., Zhang, W., Liu, R., Ni, T., Cui, B., Lei, Y., Du, J., Ai, D., Jiang, H., et al. (2023) · Diabetes · doi:10.2337/db23-0368 · Cited by 39
Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling
Kim, H., Liu, Y., Kim, J. J., Kim, Y., Klouda, T. M., Fisch, S., Baek, S. H., Liu, T., Dahlberg, S. E., Hu, C., et al. (2024) · EMBO Reports · doi:10.1038/s44319-023-00054-w · Cited by 35
“…were based on Acta2, Myh11, Tagln, Mylk, Mcam ,; ECs as clusters 1, 3, 4, 6, 15, 23, 25, and 34 were based on Cdh5, Pecam1, vWf , Flt1 ; the fi broblast markers as cluater 13, 18, 19, 20, 22 were based on S100a4, Col3a1 , and Pdgfra (Baek et al, 2022; Lendahl et al, 2022; Vanlandewijck et al, 2018).”
Atp13a5 Marker Reveals Pericyte Specification in the Mouse Central Nervous System
Guo, X., Xia, S., Ge, T., Lin, Y., Hu, S. X., Wu, H., Xie, X., Zhang, B., Zhang, S., Zeng, J., et al. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.0727-24.2024 · Cited by 35
“The developmental origin of pericytes seems to be rather complex (Yamazaki and Mukouyama, 2018); and their heterogeneity has only been con fi rmed between central and peripheral tissues, but not within the CNS (Vanlandewijck et al., 2018).”
Matera, A., Compagnion, A.-C., Pedicone, C., Kotah, J. M., Ivanov, A., Monsorno, K., Labouèbe, G., Leggio, L., Pereira-Iglesias, M., Beule, D., et al. (2025) · Immunity · doi:10.1016/j.immuni.2024.11.003 · Cited by 34
Pericyte transplantation improves skeletal muscle recovery following hindlimb immobilization
Munroe, M., Dvoretskiy, S., Lopez, A., Leong, J., Dyle, M. C., Kong, H., Adams, C. M., & Boppart, M. D. (2019) · The FASEB Journal · doi:10.1096/fj.201802580r · Cited by 33
“The recent verification of chondroitin sulfate proteoglycan (Cspg4 or neural-glial antigen 2, NG2) and melanoma cell adhesion molecule (CD146) expression on the pericyte using single-cell transcriptomic analysis is a step in the right direction toward investigation of cell function (37).”
Vascular control of the CO2/H+-dependent drive to breathe
Cleary, C. M., Moreira, T. S., Takakura, A. C. T., et al. (2020) · eLife · doi:10.7554/elife.59499 · Cited by 33
Central Nervous System Fibroblast-Like Cells in Stroke and Other Neurological Disorders
Xu, L., & Yao, Y. (2021) · Stroke · doi:10.1161/strokeaha.120.033431 · Cited by 34
Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice
Abe, Y., Kwon, S., Oishi, M., Unekawa, M., Takata, N., Seki, F., Koyama, R., Abe, M., Sakimura, K., Masamoto, K., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109427 · Cited by 29
Mlc1-Expressing Perivascular Astrocytes Promote Blood–Brain Barrier Integrity
Morales, J. E., De, A., Miller, A. A., Chen, Z., & McCarty, J. H. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1918-21.2021 · Cited by 33
Coupling of angiogenesis and odontogenesis orchestrates tooth mineralization in mice
Matsubara, T., Iga, T., Sugiura, Y., Kusumoto, D., Sanosaka, T., Tai-Nagara, I., Takeda, N., Fong, G., Ito, K., Ema, M., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211789 · Cited by 33
“8 A) based on known markers (Vanlandewijck et al., 2018; Kalucka et al., 2020) and expression of Kdr (Vegfr2) and Flt1 (Vegfr1; Fig.”
MethodCell-specific expression and function of laminin at the neurovascular unit
Nirwane, A. M., & Yao, Y. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221113027 · Cited by 36
“html).(38,108) In addition, a secretome analysis demonstrated that neural stem cell-derived pre-myelinating oligodendrocytes synthesized laminin-a2, -a4, -a5, -b1, -b2, -b3, -c1, and -c2.”
BackgroundInfluentialYou, T.-Y., Dong, Q., & Cui, M. (2022) · Aging and Disease · doi:10.14336/ad.2022.1204 · Cited by 33
“6/9/12a/12b [43] and regulators of myosin phosphorylation state [44] by single-cell RNA-seq and other transcriptomic analyses.”
BackgroundZi, H., Peng, X., Cao, J., Xie, T., Liu, T., Li, H., Bu, J., Du, J., & Li, J. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113652 · Cited by 35
Vázquez-Liébanas, E., Mocci, G., Li, W., Laviña, B., Reddy, A., O’Connor, C., Hudson, N., Elbeck, Z., Nikoloudis, I., Gaengel, K., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113911 · Cited by 32
Self-citationBernier, L., Hefendehl, J. K., Scott, R. W., Tung, L. W., Lewis, C. B., Soliman, H., Simm, S., Dissing‐Olesen, L., Hofmann, J. C., Guo, D., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01872-y · Cited by 38
Chaves, C., Campanelli, F., Chapy, H., Gomez-Zepeda, D., Glacial, F., Smirnova, M., Taghi, M., Pallud, J., Perrière, N., Declèves, X., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12040308 · Cited by 23
“According to a vascular single-cell transcriptomics study, MATE1 and OCT3 are mainly or exclusively detected in perivascular fibroblast-like cells, that are present in all brain vessel types, except brain capillaries [38].”
MethodVascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies
Bondareva, O., & Sheikh, B. N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134688 · Cited by 31
“In contrast, arteriole and arterial smooth muscle cells make up the second mural cell cluster and express high levels of Myh11, Acta2 and Myl9 [3].”
BackgroundMethodInfluentialThree-dimensional induced pluripotent stem-cell models of human brain angiogenesis
Linville, R. M., Arevalo, D., Maressa, J. C., Zhao, N., & Searson, P. C. (2020) · Microvascular Research · doi:10.1016/j.mvr.2020.104042 · Cited by 31
Luptáková, D., Vallianatou, T., Nilsson, A., Shariatgorji, M., Hammarlund‐Udenaes, M., Loryan, I., & Andrén, P. E. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01267-y · Cited by 36
TRPV4: A trigger of pathological RhoA activation in neurological disease
Bagnell, A. M., Sumner, C. J., & McCray, B. A. (2022) · BioEssays · doi:10.1002/bies.202100288 · Cited by 31
Nirwane, A. M., & Yao, Y. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04322-1 · Cited by 35
“The most widely used pericyte marker PDGFRβ also labels vSMCs and fibroblasts [16, 17], which exert important functions in injury resolution [18, 19].”
BackgroundMethodPericytes: The lung-forgotten cell type
Garrison, A. T., Bignold, R. E., Wu, X., & Johnson, J. R. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1150028 · Cited by 41
“The markers used to characterise pericytes vary depending on the location of the cell–in terms of organotypicity, there are clear differences between brain pericytes and lung pericytes (Vanlandewijck et al., 2018).”
BackgroundThe pial vasculature of the mouse develops according to a sensory-independent program
Adams, M. D., Winder, A. T., Blinder, P., & Drew, P. J. (2018) · Scientific Reports · doi:10.1038/s41598-018-27910-3 · Cited by 30
Yang, J. M., Jung, S. Y., Kim, M. S., Lee, S. W., Yon, D. K., Shin, J. I., & Lee, J. Y. (2024) · Ophthalmology · doi:10.1016/j.ophtha.2024.07.008 · Cited by 37
G Protein-Coupled Receptors in the Mammalian Blood-Brain Barrier
Pluimer, B. R., Colt, M., & Zhao, Z. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00139 · Cited by 33
Wang, K., Zhang, H., He, Y., Jiang, Q., Tanaka, Y., Park, I., Pober, J. S., Wang, M., & Zhou, H. J. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314586 · Cited by 33
Bulut, G. B., Alencar, G. F., Owsiany, K. M., Nguyen, A. T., Karnewar, S., Haskins, R. M., Waller, L. K., Cherepanova, O. A., Deaton, R. A., Shankman, L. S., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314703 · Cited by 31
Rosehart, A. C., Longden, T. A., Weir, N., Fontaine, J. T., Joutel, A., & Dabertrand, F. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.695965 · Cited by 30
Hansen, L., Lohfink, N., Vutukuri, R., Kestner, R.-I., Trautmann, S., Hecht, M., Wagner, P. V., Spitzer, D., Khel, M. I., Macas, J., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0188-21.2021 · Cited by 33
方浩), (., 亚娜), (., 君君), (., 陆军), (., 京晶), (., 勇), (., 丰原), (., & 清), (. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.317093 · Cited by 32
Kenney, H. M., Wu, C., Loiselle, A. E., Xing, L., Ritchlin, C. T., & Schwarz, E. M. (2022) · Arthritis Research & Therapy · doi:10.1186/s13075-022-02730-z · Cited by 32
Gagliano, G., Monteverdi, A., Casali, S., Laforenza, U., Wheeler‐Kingshott, C. A. M. G., D'Angelo, E. U., & Mapelli, L. (2022) · Cells · doi:10.3390/cells11061047 · Cited by 36
“Additional mechanisms as intrinsic vascular properties are involved as well [12] and might contribute to region-specific differences [13].”
Central Nervous System Pericytes Contribute to Health and Disease
Girolamo, F., Errede, M., Bizzoca, A., Virgintino, D., & Ribatti, D. (2022) · Cells · doi:10.3390/cells11101707 · Cited by 32
“Single cell studies profiling of brain- and lung-derived PCs support this view [50,51].”
ResultIncreased CSF-decorin predicts brain pathological changes driven by Alzheimer’s Aβ amyloidosis
Jiang, R., Smailović, U., Haytural, H., Tijms, B. M., Li, H., Haret, R. M., Shevchenko, G., Chen, G., Abelein, A., Gobom, J., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01398-5 · Cited by 32
“Interestingly, decorin and lumican are highly expressed in the recently identified vascular cell type fibroblast-like cells which reside within the perivascular Virchow–Robin space in the mouse brain [32].”
BackgroundCellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult
Arostegui, M., Scott, R. W., Böse, K., & Underhill, T. M. (2022) · Nature Communications · doi:10.1038/s41467-022-32695-1 · Cited by 34
The Pathology of Primary Familial Brain Calcification: Implications for Treatment
Xu, X., Sun, H., Luo, J., Cheng, X., Lv, W., Luo, W. F., Chen, W., Xiong, Z., & Liu, J. Y. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00980-0 · Cited by 32
“1) [56], and is mainly localized to the endoplasmic reticulum [24].”
BackgroundCrouch, E. E., Joseph, T., Marsan, E., & Huang, E. J. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.04.007 · Cited by 34
“In the adult mouse brain, tip and mitotic cells could no longer be identified [31].”
InfluentialNotch-mediated cellular interactions between vascular cells
Cuervo, H., Mühleder, S., García-Gónzalez, I., & Benedito, R. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102254 · Cited by 32
The phenomenon of clasmatodendrosis
Balaban, D. T., Miyawaki, E. K., Bhattacharyya, S., & Torre, M. (2021) · Heliyon · doi:10.1016/j.heliyon.2021.e07605 · Cited by 30
Nicoletti, C., Wei, X., Etxaniz, U., D’Ercole, C., Madaro, L., Perera, R. J., & Puri, P. (2023) · iScience · doi:10.1016/j.isci.2023.107114 · Cited by 31
Gao, S., Shen, R., Li, J., Jiang, Y., Sun, H., Wu, X., Li, X., Miao, C., He, M., Wang, J., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2410564121 · Cited by 31
“Utilizing public brain single - cell sequencing databases ( 57 ), we identified several genes specifically expressed in microglia and analyzed their expression in the hippocampus after CLP ( Fig.”
Chen, X., Luo, X., Yin, W., Cui, W., He, Y., Tian, T., & Lin, Y. (2025) · ACS Nano · doi:10.1021/acsnano.5c03945 · Cited by 39
Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells
Jeske, R., Albo, J., Marzano, M., Bejoy, J., & Li, Y. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2020.0091 · Cited by 33
“Some other markers are also identified, including ZIC1 (gene encoding Zic family member 1), ABCC9 (gene encoding ATP-binding cassette subfamily C member 9), and KCNJ8.(46,48) All these markers can be used as a panel to differentiate brain PCs from other mural cells.”
BackgroundHe, Y., Tacconi, C., Dieterich, L. C., Kim, J., Restivo, G., Gousopoulos, E., Lindenblatt, N., Levesque, M. P., Claassen, M., & Detmar, M. J. (2022) · Cells · doi:10.3390/cells11071111 · Cited by 30
“decoded specific molecular signatures of ECs along the arteriovenous axis in adult mouse brain and illuminated gradual transcriptomic changes that transit from arteries along capillaries towards the veins [13].”
BackgroundPalhol, J. S. C., Balia, M., Terán, F. S.-R., Labarchède, M., Gontier, É., & Battefeld, A. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00425-4 · Cited by 30
“Oligodendrocytes could be intrinsically primed to attach to the basement membrane via laminin-α2 (Lama2), which is expressed in oligodendrocytes and plays a role in myelination and OPC maturation [13, 40, 41].”
BackgroundResultInfluentialZarodniuk, M., Steele, A., Lü, X., Li, J., & Datta, M. (2023) · npj Genomic Medicine · doi:10.1038/s41525-023-00381-w · Cited by 32
“We did not detect any stromal cells in HGPTs which our previous analysis identi fi ed to be ECM hi -enriched which could be ascribed to variability in cell isolation protocols, since detachment of cells embedded in the basement membrane requires stronger tissue dissociation methods 28,35 .”
Sullivan, J. M., Bagnell, A. M., Alevy, J., Avila, E. M., Mihaljević, L., Saavedra-Rivera, P. C., Kong, L., Huh, J. S., McCray, B. A., Aisenberg, W. H., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adk1358 · Cited by 29
“S9, C to I), consistent with recent single-cell RNA sequencing (scRNA-seq) ( 22 – 27 ) and electrophysiology ( 28 ) studies.”
MethodResultMechanosensory entities and functionality of endothelial cells
Mierke, C. T. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1446452 · Cited by 36
Interleukin-34-dependent perivascular macrophages promote vascular function in the brain
Hove, H. V., Glück, C., Mildenberger, W., Petrova, E., Maheshwari, U., Häne, P., Kreiner, V., Bijnen, M., Mussak, C., Utz, S. G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.003 · Cited by 35
Self-citationLi, R., & Quon, G. (2019) · Genome biology · doi:10.1186/s13059-019-1806-0 · Cited by 30
Lysolipids in Vascular Development, Biology, and Disease
Engelbrecht, E., MacRae, C. A., & Hla, T. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.305565 · Cited by 31
Lin, W.-W., Xu, L., Chen, Y., Go, K., Sun, C., & Zhu, Y. (2021) · BioMed Research International · doi:10.1155/2021/7643209 · Cited by 29
“The single-cell RNA-seq dataset of mouse brain vessels was downloaded from GEO (GSE98816).”
BackgroundMethodInfluentialIntegrated molecular analysis identifies a conserved pericyte gene signature in zebrafish
Shih, Y.-H., Portman, D., Idrizi, F., Grosse, A. S., & Lawson, N. D. (2021) · Development · doi:10.1242/dev.200189 · Cited by 27
Kato, T., Manabe, R.-I., Igarashi, H., Kametani, F., Hirokawa, S., Sekine, Y., Fujita, N., Saito, S., Kawashima, Y., Hatano, Y., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci140555 · Cited by 32
Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C
Huuskonen, M. T., Wang, Y., Nikolakopoulou, A. M., Montagne, A., Dai, Z., Lazić, D., Sagare, A. P., Zhao, Z., Fernández, J. A., Griffin, J. H., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20211372 · Cited by 30
“3K3A-APC is protective in rodent models of brain injury (Walker et al., 2010), including ALS (Shi et al., 2019; Zhong et al., 2009) and multiple sclerosis (Han et al., 2008).”
BackgroundNatarajan, V., Ha, S., Delgado, A., Jacobson, R. I., Alhalhooly, L., Choi, Y., & Kim, J. (2022) · Cancers · doi:10.3390/cancers14102448 · Cited by 33
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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