Single-cell dissection of the human brain vasculature
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/143722 |
| _version_ | 1811076186977075200 |
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| author | Garcia, Francisco J Sun, Na Lee, Hyeseung Godlewski, Brianna Mathys, Hansruedi Galani, Kyriaki Zhou, Blake Jiang, Xueqiao Ng, Ayesha P Mantero, Julio Tsai, Li-Huei Bennett, David A Sahin, Mustafa Kellis, Manolis Heiman, Myriam |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Garcia, Francisco J Sun, Na Lee, Hyeseung Godlewski, Brianna Mathys, Hansruedi Galani, Kyriaki Zhou, Blake Jiang, Xueqiao Ng, Ayesha P Mantero, Julio Tsai, Li-Huei Bennett, David A Sahin, Mustafa Kellis, Manolis Heiman, Myriam |
| author_sort | Garcia, Francisco J |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:17:41Z |
| format | Article |
| id | mit-1721.1/143722 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:17:41Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1437222023-04-14T15:20:47Z Single-cell dissection of the human brain vasculature Garcia, Francisco J Sun, Na Lee, Hyeseung Godlewski, Brianna Mathys, Hansruedi Galani, Kyriaki Zhou, Blake Jiang, Xueqiao Ng, Ayesha P Mantero, Julio Tsai, Li-Huei Bennett, David A Sahin, Mustafa Kellis, Manolis Heiman, Myriam Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory 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. 2022-07-13T17:44:29Z 2022-07-13T17:44:29Z 2022 2022-07-13T17:16:02Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/143722 Garcia, Francisco J, Sun, Na, Lee, Hyeseung, Godlewski, Brianna, Mathys, Hansruedi et al. 2022. "Single-cell dissection of the human brain vasculature." Nature, 603 (7903). en 10.1038/S41586-022-04521-7 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC bioRxiv |
| spellingShingle | Garcia, Francisco J Sun, Na Lee, Hyeseung Godlewski, Brianna Mathys, Hansruedi Galani, Kyriaki Zhou, Blake Jiang, Xueqiao Ng, Ayesha P Mantero, Julio Tsai, Li-Huei Bennett, David A Sahin, Mustafa Kellis, Manolis Heiman, Myriam Single-cell dissection of the human brain vasculature |
| title | Single-cell dissection of the human brain vasculature |
| title_full | Single-cell dissection of the human brain vasculature |
| title_fullStr | Single-cell dissection of the human brain vasculature |
| title_full_unstemmed | Single-cell dissection of the human brain vasculature |
| title_short | Single-cell dissection of the human brain vasculature |
| title_sort | single cell dissection of the human brain vasculature |
| url | https://hdl.handle.net/1721.1/143722 |
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