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Single-cell dissection of the human brain vasculature

Author

Listed:
  • Francisco J. Garcia

    (MIT
    Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

  • Na Sun

    (Broad Institute of MIT and Harvard
    MIT
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Hyeseung Lee

    (Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

  • Brianna Godlewski

    (Boston Children’s Hospital
    Harvard Medical School)

  • Hansruedi Mathys

    (Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard
    University of Pittsburgh School of Medicine)

  • Kyriaki Galani

    (Broad Institute of MIT and Harvard
    MIT
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Blake Zhou

    (Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

  • Xueqiao Jiang

    (Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

  • Ayesha P. Ng

    (Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

  • Julio Mantero

    (Broad Institute of MIT and Harvard
    MIT
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Li-Huei Tsai

    (MIT
    Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

  • David A. Bennett

    (Rush University Medical Center)

  • Mustafa Sahin

    (Boston Children’s Hospital
    Harvard Medical School)

  • Manolis Kellis

    (Broad Institute of MIT and Harvard
    MIT
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Myriam Heiman

    (MIT
    Picower Institute for Learning and Memory
    Broad Institute of MIT and Harvard)

Abstract

Despite the importance of the cerebrovasculature in maintaining normal brain physiology and in understanding neurodegeneration and drug delivery to the central nervous system1, human cerebrovascular cells remain poorly characterized owing to their sparsity and dispersion. Here we perform single-cell characterization of the human cerebrovasculature using both ex vivo fresh tissue experimental enrichment and post mortem in silico sorting of human cortical tissue samples. We capture 16,681 cerebrovascular nuclei across 11 subtypes, including endothelial cells, mural cells and three distinct subtypes of perivascular fibroblast along the vasculature. We uncover human-specific expression patterns along the arteriovenous axis and determine previously uncharacterized cell-type-specific markers. We use these human-specific signatures to study changes in 3,945 cerebrovascular cells from patients with Huntington’s disease, which reveal activation of innate immune signalling in vascular and glial cell types and a concomitant reduction in the levels of proteins critical for maintenance of blood–brain barrier integrity. Finally, our study provides a comprehensive molecular atlas of the human cerebrovasculature to guide future biological and therapeutic studies.

Suggested Citation

  • Francisco J. Garcia & Na Sun & Hyeseung Lee & Brianna Godlewski & Hansruedi Mathys & Kyriaki Galani & Blake Zhou & Xueqiao Jiang & Ayesha P. Ng & Julio Mantero & Li-Huei Tsai & David A. Bennett & Must, 2022. "Single-cell dissection of the human brain vasculature," Nature, Nature, vol. 603(7903), pages 893-899, March.
    • Handle: RePEc:nat:nature:v:603:y:2022:i:7903:d:10.1038_s41586-022-04521-7
    DOI: 10.1038/s41586-022-04521-7
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    Citations

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    Cited by:

    1. Ryan G. Lim & Osama Al-Dalahmah & Jie Wu & Maxwell P. Gold & Jack C. Reidling & Guomei Tang & Miriam Adam & David K. Dansu & Hye-Jin Park & Patrizia Casaccia & Ricardo Miramontes & Andrea M. Reyes-Ort, 2022. "Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    2. Stergios Tsartsalis & Hannah Sleven & Nurun Fancy & Frank Wessely & Amy M. Smith & Nanet Willumsen & To Ka Dorcas Cheung & Michal J. Rokicki & Vicky Chau & Eseoghene Ifie & Combiz Khozoie & Olaf Ansor, 2024. "A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Ayano Matsushima & Sergio Sebastian Pineda & Jill R. Crittenden & Hyeseung Lee & Kyriakitsa Galani & Julio Mantero & Geoffrey Tombaugh & Manolis Kellis & Myriam Heiman & Ann M. Graybiel, 2023. "Transcriptional vulnerabilities of striatal neurons in human and rodent models of Huntington’s disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Nicola A. Kearns & Artemis Iatrou & Daniel J. Flood & Sashini Tissera & Zachary M. Mullaney & Jishu Xu & Chris Gaiteri & David A. Bennett & Yanling Wang, 2023. "Dissecting the human leptomeninges at single-cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Paula Punzon-Jimenez & Alba Machado-Lopez & Raul Perez-Moraga & Jaime Llera-Oyola & Daniela Grases & Marta Galvez-Viedma & Mustafa Sibai & Elena Satorres-Perez & Susana Lopez-Agullo & Rafael Badenes &, 2024. "Effect of aging on the human myometrium at single-cell resolution," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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