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Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging
Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged card...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740196/ https://www.ncbi.nlm.nih.gov/pubmed/35004685 http://dx.doi.org/10.3389/fcell.2021.786496 |
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author | Ge, Fei Pan, Qi Qin, Yue Jia, Mengping Ruan, Chengchao Wei, Xiangxiang Jing, Qing Zhi, Xiuling Wang, Xinhong Jiang, Lindi Osto, Elena Guo, Jieyu Meng, Dan |
author_facet | Ge, Fei Pan, Qi Qin, Yue Jia, Mengping Ruan, Chengchao Wei, Xiangxiang Jing, Qing Zhi, Xiuling Wang, Xinhong Jiang, Lindi Osto, Elena Guo, Jieyu Meng, Dan |
author_sort | Ge, Fei |
collection | PubMed |
description | Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging. |
format | Online Article Text |
id | pubmed-8740196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87401962022-01-08 Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging Ge, Fei Pan, Qi Qin, Yue Jia, Mengping Ruan, Chengchao Wei, Xiangxiang Jing, Qing Zhi, Xiuling Wang, Xinhong Jiang, Lindi Osto, Elena Guo, Jieyu Meng, Dan Front Cell Dev Biol Cell and Developmental Biology Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging. Frontiers Media S.A. 2021-12-24 /pmc/articles/PMC8740196/ /pubmed/35004685 http://dx.doi.org/10.3389/fcell.2021.786496 Text en Copyright © 2021 Ge, Pan, Qin, Jia, Ruan, Wei, Jing, Zhi, Wang, Jiang, Osto, Guo and Meng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Ge, Fei Pan, Qi Qin, Yue Jia, Mengping Ruan, Chengchao Wei, Xiangxiang Jing, Qing Zhi, Xiuling Wang, Xinhong Jiang, Lindi Osto, Elena Guo, Jieyu Meng, Dan Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging |
title | Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging |
title_full | Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging |
title_fullStr | Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging |
title_full_unstemmed | Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging |
title_short | Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging |
title_sort | single-cell analysis identify transcription factor bach1 as a master regulator gene in vascular cells during aging |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740196/ https://www.ncbi.nlm.nih.gov/pubmed/35004685 http://dx.doi.org/10.3389/fcell.2021.786496 |
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