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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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