A single-cell atlas of the normal and malformed human brain vasculature
Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult huma...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2022-03, Vol.375 (6584), p.eabi7377-eabi7377 |
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| creator | Winkler, Ethan A Kim, Chang N Ross, Jayden M Garcia, Joseph H Gil, Eugene Oh, Irene Chen, Lindsay Q Wu, David Catapano, Joshua S Raygor, Kunal Narsinh, Kazim Kim, Helen Weinsheimer, Shantel Cooke, Daniel L Walcott, Brian P Lawton, Michael T Gupta, Nalin Zlokovic, Berislav V Chang, Edward F Abla, Adib A Lim, Daniel A Nowakowski, Tomasz J |
| description | Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations. |
| doi_str_mv | 10.1126/science.abi7377 |
| format | Article |
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Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abi7377</identifier><identifier>PMID: 35084939</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Adult ; Angiogenesis ; Arteries ; Biomarkers ; Blood vessels ; Blood Vessels - cytology ; Blood Vessels - pathology ; Blood Vessels - physiology ; Blood Vessels - physiopathology ; Brain ; Brain - blood supply ; Brain mapping ; Capillaries ; Cell culture ; Cell interactions ; Cells, Cultured ; Cerebral Cortex - blood supply ; Cerebral Hemorrhage - pathology ; Cerebral Hemorrhage - physiopathology ; Cerebrovascular Circulation ; Cerebrovascular diseases ; Comparative analysis ; Crosstalk ; Death ; Depletion ; Drug development ; Endothelial cells ; Endothelial Cells - cytology ; Endothelial Cells - pathology ; Endothelial Cells - physiology ; Endothelium ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - physiology ; Fluorescence ; Fluorescence in situ hybridization ; Gene expression ; Gene sequencing ; Heterogeneity ; Humans ; Immune system ; Inflammation ; Intracranial Arteriovenous Malformations - metabolism ; Intracranial Arteriovenous Malformations - pathology ; Monocytes ; Monocytes - cytology ; Monocytes - physiology ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - pathology ; Muscle, Smooth, Vascular - physiology ; Muscles ; Neuronal-glial interactions ; Pericytes ; Pericytes - cytology ; Pericytes - physiology ; Perturbation ; RNA-Seq ; Single-Cell Analysis ; Smooth muscle ; Spatial distribution ; Specialization ; Stroke ; Therapeutic targets ; Transcription ; Transcriptome ; Vascular diseases ; Young adults ; Zonation</subject><ispartof>Science (American Association for the Advancement of Science), 2022-03, Vol.375 (6584), p.eabi7377-eabi7377</ispartof><rights>Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-56a902b3fc70ea454f62bef7ff3fa707be8d27b4201b2212e732fc780c9bfc3d3</citedby><cites>FETCH-LOGICAL-c533t-56a902b3fc70ea454f62bef7ff3fa707be8d27b4201b2212e732fc780c9bfc3d3</cites><orcidid>0000-0002-7908-7107 ; 0000-0002-7127-9534 ; 0000-0002-3694-413X ; 0000-0001-7921-4447 ; 0000-0002-2019-5461 ; 0000-0002-6802-8232 ; 0000-0002-5517-7706 ; 0000-0003-2480-4700 ; 0000-0002-6941-2295 ; 0000-0002-9030-3667 ; 0000-0003-2345-4964 ; 0000-0001-7486-9110 ; 0000-0002-1937-354X ; 0000-0001-7221-3425</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,2870,2871,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35084939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Winkler, Ethan A</creatorcontrib><creatorcontrib>Kim, Chang N</creatorcontrib><creatorcontrib>Ross, Jayden M</creatorcontrib><creatorcontrib>Garcia, Joseph H</creatorcontrib><creatorcontrib>Gil, Eugene</creatorcontrib><creatorcontrib>Oh, Irene</creatorcontrib><creatorcontrib>Chen, Lindsay Q</creatorcontrib><creatorcontrib>Wu, David</creatorcontrib><creatorcontrib>Catapano, Joshua S</creatorcontrib><creatorcontrib>Raygor, Kunal</creatorcontrib><creatorcontrib>Narsinh, Kazim</creatorcontrib><creatorcontrib>Kim, Helen</creatorcontrib><creatorcontrib>Weinsheimer, Shantel</creatorcontrib><creatorcontrib>Cooke, Daniel L</creatorcontrib><creatorcontrib>Walcott, Brian P</creatorcontrib><creatorcontrib>Lawton, Michael T</creatorcontrib><creatorcontrib>Gupta, Nalin</creatorcontrib><creatorcontrib>Zlokovic, Berislav V</creatorcontrib><creatorcontrib>Chang, Edward F</creatorcontrib><creatorcontrib>Abla, Adib A</creatorcontrib><creatorcontrib>Lim, Daniel A</creatorcontrib><creatorcontrib>Nowakowski, Tomasz J</creatorcontrib><title>A single-cell atlas of the normal and malformed human brain vasculature</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.</description><subject>Adult</subject><subject>Angiogenesis</subject><subject>Arteries</subject><subject>Biomarkers</subject><subject>Blood vessels</subject><subject>Blood Vessels - cytology</subject><subject>Blood Vessels - pathology</subject><subject>Blood Vessels - physiology</subject><subject>Blood Vessels - physiopathology</subject><subject>Brain</subject><subject>Brain - blood supply</subject><subject>Brain mapping</subject><subject>Capillaries</subject><subject>Cell culture</subject><subject>Cell interactions</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - blood supply</subject><subject>Cerebral Hemorrhage - pathology</subject><subject>Cerebral Hemorrhage - physiopathology</subject><subject>Cerebrovascular Circulation</subject><subject>Cerebrovascular diseases</subject><subject>Comparative analysis</subject><subject>Crosstalk</subject><subject>Death</subject><subject>Depletion</subject><subject>Drug development</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - pathology</subject><subject>Endothelial Cells - physiology</subject><subject>Endothelium</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - physiology</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Intracranial Arteriovenous Malformations - metabolism</subject><subject>Intracranial Arteriovenous Malformations - pathology</subject><subject>Monocytes</subject><subject>Monocytes - cytology</subject><subject>Monocytes - physiology</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Muscles</subject><subject>Neuronal-glial interactions</subject><subject>Pericytes</subject><subject>Pericytes - cytology</subject><subject>Pericytes - physiology</subject><subject>Perturbation</subject><subject>RNA-Seq</subject><subject>Single-Cell Analysis</subject><subject>Smooth muscle</subject><subject>Spatial distribution</subject><subject>Specialization</subject><subject>Stroke</subject><subject>Therapeutic targets</subject><subject>Transcription</subject><subject>Transcriptome</subject><subject>Vascular diseases</subject><subject>Young adults</subject><subject>Zonation</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFLAzEQhYMotlbP3iTgxcu2Saa72VyEUrQKBS96DkmatFu22ZrsFvz3prQW9TRk5pvHvDyEbikZUsqKUTSV9cYOla44cH6G-pSIPBOMwDnqEwJFVhKe99BVjGtC0kzAJepBTsqxANFHswmOlV_WNjO2rrFqaxVx43C7stg3YaNSzy9wqi697AKvuo3yWAdVebxT0XS1artgr9GFU3W0N8c6QB_PT-_Tl2z-NnudTuaZyQHaLC-UIEyDM5xYNc7HrmDaOu4cOMUJ17ZcMK7HjFDNGGWWA0tsSYzQzsACBujxoLvtdDrHWN8GVcttqDYqfMlGVfLvxFcruWx2shQip7xMAg9HgdB8dja2clPFvXflbdNFyQoGZQmc5Qm9_4eumy74ZC9RkP6VC0oSNTpQJjQxButOx1Ai9yHJY0jyGFLauPvt4cT_pALfukGQog</recordid><startdate>20220304</startdate><enddate>20220304</enddate><creator>Winkler, Ethan A</creator><creator>Kim, Chang N</creator><creator>Ross, Jayden M</creator><creator>Garcia, Joseph H</creator><creator>Gil, Eugene</creator><creator>Oh, Irene</creator><creator>Chen, Lindsay Q</creator><creator>Wu, David</creator><creator>Catapano, Joshua S</creator><creator>Raygor, Kunal</creator><creator>Narsinh, Kazim</creator><creator>Kim, Helen</creator><creator>Weinsheimer, Shantel</creator><creator>Cooke, Daniel L</creator><creator>Walcott, Brian P</creator><creator>Lawton, Michael T</creator><creator>Gupta, Nalin</creator><creator>Zlokovic, Berislav V</creator><creator>Chang, Edward F</creator><creator>Abla, Adib A</creator><creator>Lim, Daniel A</creator><creator>Nowakowski, Tomasz J</creator><general>The American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7908-7107</orcidid><orcidid>https://orcid.org/0000-0002-7127-9534</orcidid><orcidid>https://orcid.org/0000-0002-3694-413X</orcidid><orcidid>https://orcid.org/0000-0001-7921-4447</orcidid><orcidid>https://orcid.org/0000-0002-2019-5461</orcidid><orcidid>https://orcid.org/0000-0002-6802-8232</orcidid><orcidid>https://orcid.org/0000-0002-5517-7706</orcidid><orcidid>https://orcid.org/0000-0003-2480-4700</orcidid><orcidid>https://orcid.org/0000-0002-6941-2295</orcidid><orcidid>https://orcid.org/0000-0002-9030-3667</orcidid><orcidid>https://orcid.org/0000-0003-2345-4964</orcidid><orcidid>https://orcid.org/0000-0001-7486-9110</orcidid><orcidid>https://orcid.org/0000-0002-1937-354X</orcidid><orcidid>https://orcid.org/0000-0001-7221-3425</orcidid></search><sort><creationdate>20220304</creationdate><title>A single-cell atlas of the normal and malformed human brain vasculature</title><author>Winkler, Ethan A ; Kim, Chang N ; Ross, Jayden M ; Garcia, Joseph H ; Gil, Eugene ; Oh, Irene ; Chen, Lindsay Q ; Wu, David ; Catapano, Joshua S ; Raygor, Kunal ; Narsinh, Kazim ; Kim, Helen ; Weinsheimer, Shantel ; Cooke, Daniel L ; Walcott, Brian P ; Lawton, Michael T ; Gupta, Nalin ; Zlokovic, Berislav V ; Chang, Edward F ; Abla, Adib A ; Lim, Daniel A ; Nowakowski, Tomasz J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-56a902b3fc70ea454f62bef7ff3fa707be8d27b4201b2212e732fc780c9bfc3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Angiogenesis</topic><topic>Arteries</topic><topic>Biomarkers</topic><topic>Blood vessels</topic><topic>Blood Vessels - cytology</topic><topic>Blood Vessels - pathology</topic><topic>Blood Vessels - physiology</topic><topic>Blood Vessels - physiopathology</topic><topic>Brain</topic><topic>Brain - blood supply</topic><topic>Brain mapping</topic><topic>Capillaries</topic><topic>Cell culture</topic><topic>Cell interactions</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - blood supply</topic><topic>Cerebral Hemorrhage - pathology</topic><topic>Cerebral Hemorrhage - physiopathology</topic><topic>Cerebrovascular Circulation</topic><topic>Cerebrovascular diseases</topic><topic>Comparative analysis</topic><topic>Crosstalk</topic><topic>Death</topic><topic>Depletion</topic><topic>Drug development</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - pathology</topic><topic>Endothelial Cells - physiology</topic><topic>Endothelium</topic><topic>Fibroblasts</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - physiology</topic><topic>Fluorescence</topic><topic>Fluorescence in situ hybridization</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Immune system</topic><topic>Inflammation</topic><topic>Intracranial Arteriovenous Malformations - 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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2022-03, Vol.375 (6584), p.eabi7377-eabi7377 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8995178 |
| source | American Association for the Advancement of Science; MEDLINE |
| subjects | Adult Angiogenesis Arteries Biomarkers Blood vessels Blood Vessels - cytology Blood Vessels - pathology Blood Vessels - physiology Blood Vessels - physiopathology Brain Brain - blood supply Brain mapping Capillaries Cell culture Cell interactions Cells, Cultured Cerebral Cortex - blood supply Cerebral Hemorrhage - pathology Cerebral Hemorrhage - physiopathology Cerebrovascular Circulation Cerebrovascular diseases Comparative analysis Crosstalk Death Depletion Drug development Endothelial cells Endothelial Cells - cytology Endothelial Cells - pathology Endothelial Cells - physiology Endothelium Fibroblasts Fibroblasts - cytology Fibroblasts - physiology Fluorescence Fluorescence in situ hybridization Gene expression Gene sequencing Heterogeneity Humans Immune system Inflammation Intracranial Arteriovenous Malformations - metabolism Intracranial Arteriovenous Malformations - pathology Monocytes Monocytes - cytology Monocytes - physiology Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - pathology Muscle, Smooth, Vascular - physiology Muscles Neuronal-glial interactions Pericytes Pericytes - cytology Pericytes - physiology Perturbation RNA-Seq Single-Cell Analysis Smooth muscle Spatial distribution Specialization Stroke Therapeutic targets Transcription Transcriptome Vascular diseases Young adults Zonation |
| title | A single-cell atlas of the normal and malformed human brain vasculature |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T06%3A55%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20single-cell%20atlas%20of%20the%20normal%20and%20malformed%20human%20brain%20vasculature&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Winkler,%20Ethan%20A&rft.date=2022-03-04&rft.volume=375&rft.issue=6584&rft.spage=eabi7377&rft.epage=eabi7377&rft.pages=eabi7377-eabi7377&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.abi7377&rft_dat=%3Cproquest_pubme%3E2623883725%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2638077910&rft_id=info:pmid/35084939&rfr_iscdi=true |