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Co-profiling reveals distinct patterns of genomic chromatin accessibility and gene expression in pulmonary hypertension caused by chronic hypoxia.

Authors :
Yu, Dongdong
Zhang, Ting
Zhou, Guangyuan
Wu, Zeang
Xiao, Rui
Zhang, Han
Liu, Bingxun
Li, Xiangpan
Ruiz, Matthieu
Dupuis, Jocelyn
Zhu, Liping
Hu, Qinghua
Source :
Respiratory Research; 4/8/2023, Vol. 24 Issue 1, p1-4, 4p
Publication Year :
2023

Abstract

Introduction: Aberrant gene expression is a key mechanism underlying pulmonary hypertension (PH) development. The alterations of genomic chromatin accessibility and their relationship with the aberrant gene expressions in PH are poorly understood. We used bulk Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) in pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxia-exposed rats mimicking group 3 human PH. Methods: Adult Sprague Dawley rats were commercially obtained from Hunan SJA (Hunan SJA Laboratory Animal Co., Changsha, China) and randomizedly allocated into four groups exposing to nomobaric hypoxia or normoxia for 1 or 28 days respectively. After the assessment of pulmonary hemodynamics, smooth muscle cells were isolated from intralobular arteries and simultaneously subjected to bulk Assay of ATAC-seq and RNA-seq. Results: Hypoxic exposure for continuous 28-days, but not for 1-day, induced established PH phenotypes in rats. ATAC-seq revealed a major distribution of differential accessibility regions (DARs) annotated to the genome in out-of-promoter regions, following 1-day or 28-days hypoxia. 1188 DAR-associated genes and 378 differentially expressed genes (DEGs) were identified in rats after exposure to 1-day hypoxia, while 238 DAR-associated genes and 452 DEGs for 28-days hypoxia. Most of the DAR-associated genes or DEGs in 1-day did not overlap with that of 28-days hypoxia. A Pearson correlation analysis indicated no significant correlation between ATAC-seq and RNA-seq. Conclusions: The alterations in genomic chromatin accessibility and genes expression of PASMCs in the initial stage of hypoxia are distinct from the established stage of hypoxia-induced PH. The genomic differential accessibility regions may not be the main mechanisms directly underlying the differentially expressed genes observed either in the initial or established stages of PH. Thus the time-course alterations of gene expression and their possible indirect link with genomic chromatin accessibility warrant more attention in mechanistic study of pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14659921
Volume :
24
Issue :
1
Database :
Complementary Index
Journal :
Respiratory Research
Publication Type :
Academic Journal
Accession number :
162969867
Full Text :
https://doi.org/10.1186/s12931-023-02389-3