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Unravelling the impact of aging on the human endothelial lncRNA transcriptome

ABSTRACT: Unravelling the impact of aging on the human endothelial lncRNA transcriptome

PROVIDER: PRJNA885487 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21757002.fastq.gz	Fastqsanger.gz
	SRR21757003.fastq.gz	Fastqsanger.gz
	SRR21757004.fastq.gz	Fastqsanger.gz
	SRR21757005.fastq.gz	Fastqsanger.gz
	SRR21757006.fastq.gz	Fastqsanger.gz

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Unravelling the impact of aging on the human endothelial lncRNA transcriptome [Young_vs_Aged RNA-seq]

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Unravelling the impact of aging on the human endothelial lncRNA transcriptome.

Project description:The incidence and prevalence of cardiovascular disease is highest among the elderly. There is a need to further understand the mechanisms behind endothelial cell aging in order to achieve vascular rejuvenation and minimize the onset of age-related vascular diseases. Long non-coding RNAs (lncRNAs) have been proposed to regulate numerous processes in the human genome, yet their function in vascular aging and their therapeutic potential remain largely unknown. This is primarily because the majority of studies investigating the impact of aging on lncRNA expression heavily rely on in vitro studies based on replicative senescence. Here, using a unique collection of young and aged endothelial cells isolated from native human arteries, we sought to characterize the age-related alterations in lncRNA expression profiles. We were able to detect a total of 4463 lncRNAs expressed in the human endothelium from which ∼17% (798) were altered in advanced age. One of the most affected lncRNAs in aging was the primate-specific, Prostate Cancer Associated Transcript (PCAT) 14. In our follow up analysis, using single molecule RNA FISH, we showed that PCAT14 is relatively abundant, localized almost exclusively in the nucleus of young endothelial cells, and silenced in the aged endothelium. Functionally, our studies proposed that downregulation of PCAT14 alters endothelial cell transcription profile and cell functions including endothelial cell migration, sprouting and inflammatory responses in vitro. Taken together, our data highlight that endothelial cell aging correlates with altered expression of lncRNAs, which could impair the endothelial regenerative capacity and enhance inflammatory phenotypes.

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Unravelling the impact of aging on the human endothelial lncRNA transcriptome [HUVEC CTL_vs_PCAT14 RNA-seq]

Project description:Gene expression profiling analysis was performed using the RNA-Seq data obtained from endothelial cells expressing or knockdown for PCAT14

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Unravelling the impact of aging on the human endothelial lncRNA transcriptome

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:The homeostasis of vascular endothelium is crucial for cardiovascular health and endothelial cell (EC) aging and dysfunction could negatively impact vascular function. Leveraging time-series transcriptomic data obtained from endothelial cells (ECs) subjected to physiological pulsatile flow versus pathophysiological oscillatory flow, we performed principal component analysis (PCA) to identify key genes contributing to divergent transcriptional states of ECs under distinct flow patterns. Through bioinformatics analysis, we identified that a long non-coding RNA (lncRNA) RAMP2- AS1 encoded on the antisense of RAMP2, a determinant of endothelial homeostasis and vascular integrity, is a novel regulator essential for EC homeostasis and function. Knockdown of RAMP2-AS1 inhibited EC angiogenesis and promoted EC senescence, as a result of extensive changes of EC transcriptome. Our study demonstrates an integrative approach to quantifying EC aging based on transcriptome changes, which also identified a number of novel regulators, including protein-coding genes and many lncRNAs involved EC functional modulation.

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