Cargando…
Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling
The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurys...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774900/ https://www.ncbi.nlm.nih.gov/pubmed/35052435 http://dx.doi.org/10.3390/genes13010095 |
_version_ | 1784636454006161408 |
---|---|
author | Dawson, Ashley Li, Yanming Li, Yang Ren, Pingping Vasquez, Hernan G. Zhang, Chen Rebello, Kimberly R. Ageedi, Waleed Azares, Alon R. Mattar, Aladdein Burchett Sheppard, Mary Burchett Lu, Hong S. Coselli, Joseph S. Cassis, Lisa A. Daugherty, Alan Shen, Ying H. LeMaire, Scott A. |
author_facet | Dawson, Ashley Li, Yanming Li, Yang Ren, Pingping Vasquez, Hernan G. Zhang, Chen Rebello, Kimberly R. Ageedi, Waleed Azares, Alon R. Mattar, Aladdein Burchett Sheppard, Mary Burchett Lu, Hong S. Coselli, Joseph S. Cassis, Lisa A. Daugherty, Alan Shen, Ying H. LeMaire, Scott A. |
author_sort | Dawson, Ashley |
collection | PubMed |
description | The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations of cell populations with increased de-differentiated proliferative SMCs compared to controls. Furthermore, there was a downregulation of MYOCD and MYH11 in SMCs, and an upregulation of COL1A1/2 in fibroblasts in MFS samples compared to controls. We also examined TGF-β signaling, an important pathway in aortic homeostasis. We found that TGFB1 was significantly upregulated in two fibroblast clusters in MFS tissues. However, TGF-β receptor genes (predominantly TGFBR2) and SMAD genes were downregulated in SMCs, fibroblasts, and ECs in MFS, indicating impairment in TGF-β signaling. In conclusion, despite upregulation of TGFB1, the rest of the canonical TGF-β pathway and mature SMCs were consistently downregulated in MFS, indicating a potential compromise of TGF-β signaling and lack of stimulus for SMC differentiation. |
format | Online Article Text |
id | pubmed-8774900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87749002022-01-21 Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling Dawson, Ashley Li, Yanming Li, Yang Ren, Pingping Vasquez, Hernan G. Zhang, Chen Rebello, Kimberly R. Ageedi, Waleed Azares, Alon R. Mattar, Aladdein Burchett Sheppard, Mary Burchett Lu, Hong S. Coselli, Joseph S. Cassis, Lisa A. Daugherty, Alan Shen, Ying H. LeMaire, Scott A. Genes (Basel) Article The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations of cell populations with increased de-differentiated proliferative SMCs compared to controls. Furthermore, there was a downregulation of MYOCD and MYH11 in SMCs, and an upregulation of COL1A1/2 in fibroblasts in MFS samples compared to controls. We also examined TGF-β signaling, an important pathway in aortic homeostasis. We found that TGFB1 was significantly upregulated in two fibroblast clusters in MFS tissues. However, TGF-β receptor genes (predominantly TGFBR2) and SMAD genes were downregulated in SMCs, fibroblasts, and ECs in MFS, indicating impairment in TGF-β signaling. In conclusion, despite upregulation of TGFB1, the rest of the canonical TGF-β pathway and mature SMCs were consistently downregulated in MFS, indicating a potential compromise of TGF-β signaling and lack of stimulus for SMC differentiation. MDPI 2021-12-30 /pmc/articles/PMC8774900/ /pubmed/35052435 http://dx.doi.org/10.3390/genes13010095 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dawson, Ashley Li, Yanming Li, Yang Ren, Pingping Vasquez, Hernan G. Zhang, Chen Rebello, Kimberly R. Ageedi, Waleed Azares, Alon R. Mattar, Aladdein Burchett Sheppard, Mary Burchett Lu, Hong S. Coselli, Joseph S. Cassis, Lisa A. Daugherty, Alan Shen, Ying H. LeMaire, Scott A. Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling |
title | Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling |
title_full | Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling |
title_fullStr | Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling |
title_full_unstemmed | Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling |
title_short | Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling |
title_sort | single-cell analysis of aneurysmal aortic tissue in patients with marfan syndrome reveals dysfunctional tgf-β signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774900/ https://www.ncbi.nlm.nih.gov/pubmed/35052435 http://dx.doi.org/10.3390/genes13010095 |
work_keys_str_mv | AT dawsonashley singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT liyanming singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT liyang singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT renpingping singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT vasquezhernang singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT zhangchen singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT rebellokimberlyr singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT ageediwaleed singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT azaresalonr singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT mattaraladdeinburchett singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT sheppardmaryburchett singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT luhongs singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT cosellijosephs singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT cassislisaa singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT daughertyalan singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT shenyingh singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling AT lemairescotta singlecellanalysisofaneurysmalaortictissueinpatientswithmarfansyndromerevealsdysfunctionaltgfbsignaling |