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| Status |
Public on Oct 01, 2020 |
| Title |
Single-cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we sought to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues.
METHODS: We performed single-cell RNA sequencing (sc-RNAseq) analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 controls (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized by using sc-RNAseq data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our sc-RNAseq data with publicly available data from genome-wide association studies (GWAS).
RESULTS: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. Generally, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than did control tissues. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our sc-RNAseq data with public GWAS data and promoter capture Hi-C data suggested that ERG (ETS [erythroblast transformation-specific] related gene) exerts an important role in maintaining normal aortic wall function.
CONCLUSIONS: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.
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| |
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| Overall design |
mRNA profiles of 3 control and 8 ATAA human aortic tissue at single cell level
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| |
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| Contributor(s) |
Li Y, Shen YH, LeMaire SA |
| Citation(s) |
33017217, 37308786 |
| Submission date |
Jul 30, 2020 |
| Last update date |
Sep 12, 2023 |
| Contact name |
Yanming Li |
| E-mail(s) |
yanming.li@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Michael E. DeBakey Department of Surgery
|
| Lab |
Aortic Disease Research Lab
|
| Street address |
One Baylor Plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (11)
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| Relations |
| BioProject |
PRJNA649846 |
| SRA |
SRP274475 |
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