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Single-cell atlas of the human brain vasculature across development, adulthood and disease.
Wälchli, Thomas; Ghobrial, Moheb; Schwab, Marc; Takada, Shigeki; Zhong, Hang; Suntharalingham, Samuel; Vetiska, Sandra; Gonzalez, Daymé Rodrigues; Wu, Ruilin; Rehrauer, Hubert; Dinesh, Anuroopa; Yu, Kai; Chen, Edward L Y; Bisschop, Jeroen; Farnhammer, Fiona; Mansur, Ann; Kalucka, Joanna; Tirosh, Itay; Regli, Luca; Schaller, Karl; Frei, Karl; Ketela, Troy; Bernstein, Mark; Kongkham, Paul; Carmeliet, Peter; Valiante, Taufik; Dirks, Peter B; Suva, Mario L; Zadeh, Gelareh; Tabar, Viviane; Schlapbach, Ralph; Jackson, Hartland W; De Bock, Katrien; Fish, Jason E; Monnier, Philippe P; Bader, Gary D; Radovanovic, Ivan.
Afiliación
  • Wälchli T; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. thomas.waelchli2@uzh.ch.
  • Ghobrial M; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. thomas.waelchli2@uzh.ch.
  • Schwab M; Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich and University Hospital Zurich, Zurich, Switzerland. thomas.waelchli2@uzh.ch.
  • Takada S; Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland. thomas.waelchli2@uzh.ch.
  • Zhong H; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Suntharalingham S; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Vetiska S; Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  • Gonzalez DR; Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
  • Wu R; Laboratory of Exercise and Health, Institute of Exercise and Health, Department of Health Sciences and Technology; Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.
  • Rehrauer H; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Dinesh A; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Yu K; Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  • Chen ELY; Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
  • Bisschop J; Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
  • Farnhammer F; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Mansur A; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Kalucka J; Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Tirosh I; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Regli L; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Schaller K; Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  • Frei K; Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
  • Ketela T; Laboratory of Exercise and Health, Institute of Exercise and Health, Department of Health Sciences and Technology; Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.
  • Bernstein M; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Kongkham P; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Carmeliet P; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Valiante T; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Dirks PB; Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Suva ML; Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland.
  • Zadeh G; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Tabar V; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
  • Schlapbach R; Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland.
  • Jackson HW; The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System, Toronto, Ontario, Canada.
  • De Bock K; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Fish JE; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
  • Monnier PP; The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System, Toronto, Ontario, Canada.
  • Bader GD; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Radovanovic I; Group Brain Vasculature and Perivascular Niche, Division of Experimental and Translational Neuroscience, Krembil Brain Institute, Krembil Research Institute, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Nature ; 632(8025): 603-613, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38987604
ABSTRACT
A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Neoplasias Encefálicas / Malformaciones Vasculares del Sistema Nervioso Central / Células Endoteliales / Feto / RNA-Seq / Análisis de Expresión Génica de una Sola Célula Límite: Adult / Female / Humans / Male Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Neoplasias Encefálicas / Malformaciones Vasculares del Sistema Nervioso Central / Células Endoteliales / Feto / RNA-Seq / Análisis de Expresión Génica de una Sola Célula Límite: Adult / Female / Humans / Male Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido