Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations
Abstract Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (...
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2025-05-01
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| author | Sohei Ito David B. Graf Yuriko Katsumata Jessica J. Moorleghen Chen Zhang Yanming Li Scott A. LeMaire Ying H. Shen Hong S. Lu Alan Daugherty Hisashi Sawada |
| author_facet | Sohei Ito David B. Graf Yuriko Katsumata Jessica J. Moorleghen Chen Zhang Yanming Li Scott A. LeMaire Ying H. Shen Hong S. Lu Alan Daugherty Hisashi Sawada |
| author_sort | Sohei Ito |
| collection | DOAJ |
| description | Abstract Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and single-cell RNA sequencing was performed. Transcriptomic analysis revealed significant changes in both SHF- and nSHF-derived SMCs following short-term AngII infusion, although differences between the origins were modest. Similarly, fibroblast transcriptomes exhibited notable changes, yet lineage-specific differences remained modest, except for a newly identified fibroblast subpopulation where extracellular matrix-related genes such as Eln and Col3a1 were downregulated in SHF-derived fibroblasts compared to nSHF-derived fibroblasts. These findings suggest that while fibroblasts in the new subcluster exhibit lineage-specific extracellular matrix-related differences, overall transcriptomic variations between SHF- and nSHF-derived cells in response to AngII remain modest during the prepathological phase of AngII-induced thoracic aortopathy. |
| format | Article |
| id | doaj-art-358e16b67b634e53a07a24072afc2c53 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-358e16b67b634e53a07a24072afc2c532025-08-20T03:10:18ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-99862-4Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterationsSohei Ito0David B. Graf1Yuriko Katsumata2Jessica J. Moorleghen3Chen Zhang4Yanming Li5Scott A. LeMaire6Ying H. Shen7Hong S. Lu8Alan Daugherty9Hisashi Sawada10Saha Cardiovascular Research Center, College of Medicine, University of KentuckySaha Cardiovascular Research Center, College of Medicine, University of KentuckyDepartment of Biostatistics, College of Public Health, College of Medicine, University of KentuckySaha Cardiovascular Research Center, College of Medicine, University of KentuckyDivision of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of MedicineDivision of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of MedicineDivision of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of MedicineDivision of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of MedicineSaha Cardiovascular Research Center, College of Medicine, University of KentuckySaha Cardiovascular Research Center, College of Medicine, University of KentuckySaha Cardiovascular Research Center, College of Medicine, University of KentuckyAbstract Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and single-cell RNA sequencing was performed. Transcriptomic analysis revealed significant changes in both SHF- and nSHF-derived SMCs following short-term AngII infusion, although differences between the origins were modest. Similarly, fibroblast transcriptomes exhibited notable changes, yet lineage-specific differences remained modest, except for a newly identified fibroblast subpopulation where extracellular matrix-related genes such as Eln and Col3a1 were downregulated in SHF-derived fibroblasts compared to nSHF-derived fibroblasts. These findings suggest that while fibroblasts in the new subcluster exhibit lineage-specific extracellular matrix-related differences, overall transcriptomic variations between SHF- and nSHF-derived cells in response to AngII remain modest during the prepathological phase of AngII-induced thoracic aortopathy.https://doi.org/10.1038/s41598-025-99862-4AortopathyAneurysmDissectionAngiotensinSmooth muscle cellsFibroblasts |
| spellingShingle | Sohei Ito David B. Graf Yuriko Katsumata Jessica J. Moorleghen Chen Zhang Yanming Li Scott A. LeMaire Ying H. Shen Hong S. Lu Alan Daugherty Hisashi Sawada Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations Scientific Reports Aortopathy Aneurysm Dissection Angiotensin Smooth muscle cells Fibroblasts |
| title | Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations |
| title_full | Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations |
| title_fullStr | Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations |
| title_full_unstemmed | Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations |
| title_short | Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations |
| title_sort | smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin ii driven transcriptional alterations |
| topic | Aortopathy Aneurysm Dissection Angiotensin Smooth muscle cells Fibroblasts |
| url | https://doi.org/10.1038/s41598-025-99862-4 |
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