Single-cell dissection of the human brain vasculature

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, Mustafa Sahin, Manolis Kellis () and Myriam Heiman ()
Additional contact information
Francisco J. Garcia: MIT
Na Sun: Broad Institute of MIT and Harvard
Hyeseung Lee: Picower Institute for Learning and Memory
Brianna Godlewski: Boston Children’s Hospital
Hansruedi Mathys: Picower Institute for Learning and Memory
Kyriaki Galani: Broad Institute of MIT and Harvard
Blake Zhou: Picower Institute for Learning and Memory
Xueqiao Jiang: Picower Institute for Learning and Memory
Ayesha P. Ng: Picower Institute for Learning and Memory
Julio Mantero: Broad Institute of MIT and Harvard
Li-Huei Tsai: MIT
David A. Bennett: Rush University Medical Center
Mustafa Sahin: Boston Children’s Hospital
Manolis Kellis: Broad Institute of MIT and Harvard
Myriam Heiman: MIT

Nature, 2022, vol. 603, issue 7903, 893-899

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-022-04521-7

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