Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations
Background: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulati...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Ovid Technologies (Wolters Kluwer Health)
2022
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| Online Access: | https://hdl.handle.net/1721.1/136197.2 |
| _version_ | 1810974439277330432 |
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| author | Kalluri, Aditya S. Vellarikkal, Shamsudheen K. Edelman, Elazer R. Nguyen, Lan Subramanian, Ayshwarya Ellinor, Patrick T. Regev, Aviv Kathiresan, Sekar Gupta, Rajat M. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Kalluri, Aditya S. Vellarikkal, Shamsudheen K. Edelman, Elazer R. Nguyen, Lan Subramanian, Ayshwarya Ellinor, Patrick T. Regev, Aviv Kathiresan, Sekar Gupta, Rajat M. |
| author_sort | Kalluri, Aditya S. |
| collection | MIT |
| description | Background: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations. Methods: We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells. Results: Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta. Conclusions: We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions. |
| first_indexed | 2024-09-23T08:23:30Z |
| format | Article |
| id | mit-1721.1/136197.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:23:30Z |
| publishDate | 2022 |
| publisher | Ovid Technologies (Wolters Kluwer Health) |
| record_format | dspace |
| spelling | mit-1721.1/136197.22024-06-13T20:08:03Z Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations Kalluri, Aditya S. Vellarikkal, Shamsudheen K. Edelman, Elazer R. Nguyen, Lan Subramanian, Ayshwarya Ellinor, Patrick T. Regev, Aviv Kathiresan, Sekar Gupta, Rajat M. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Background: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations. Methods: We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells. Results: Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta. Conclusions: We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions. 2022-03-14T17:34:08Z 2021-10-27T20:34:13Z 2022-03-14T17:34:08Z 2019-07 2018-10 2020-07-20T15:46:02Z Article http://purl.org/eprint/type/JournalArticle 0009-7322 1524-4539 https://hdl.handle.net/1721.1/136197.2 en http://dx.doi.org/10.1161/circulationaha.118.038362 Circulation Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/octet-stream Ovid Technologies (Wolters Kluwer Health) PMC |
| spellingShingle | Kalluri, Aditya S. Vellarikkal, Shamsudheen K. Edelman, Elazer R. Nguyen, Lan Subramanian, Ayshwarya Ellinor, Patrick T. Regev, Aviv Kathiresan, Sekar Gupta, Rajat M. Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations |
| title | Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations |
| title_full | Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations |
| title_fullStr | Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations |
| title_full_unstemmed | Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations |
| title_short | Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations |
| title_sort | single cell analysis of the normal mouse aorta reveals functionally distinct endothelial cell populations |
| url | https://hdl.handle.net/1721.1/136197.2 |
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