Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence

Abstract Background Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in...

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Autores principales:	Momoko Ohori, Yusuke Nakayama, Mari Ogasawara-Shimizu, Hiroyoshi Toyoshiba, Atsushi Nakanishi, Samuel Aparicio, Shinsuke Araki
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Replicative senescence HUVEC Alternative splicing Microexon MYC SIRT2 Biotechnology TP248.13-248.65 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8a3ccdb38a2246d8b51530ba78db631f
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spelling	oai:doaj.org-article:8a3ccdb38a2246d8b51530ba78db631f2021-12-05T12:17:19ZGene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence10.1186/s12864-021-08185-x1471-2164https://doaj.org/article/8a3ccdb38a2246d8b51530ba78db631f2021-12-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08185-xhttps://doaj.org/toc/1471-2164Abstract Background Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in endothelial cell senescence is lacking. Results We thoroughly described the transcriptome landscape of replicative senescent human umbilical vein endothelial cells. Genes with high connectivity showing a monotonic expression increase or decrease with the culture period were defined as hub genes in the co-expression network. Computational network analysis of these genes led to the identification of canonical and non-canonical senescence pathways, such as E2F and SIRT2 signaling, which were down-regulated in lipid metabolism, and chromosome organization processes pathways. Additionally, we showed that endothelial cell senescence involves alternative splicing. Importantly, the first and last exon types of splicing, as observed in FLT1 and ACACA, were preferentially altered among the alternatively spliced genes during endothelial senescence. We further identified novel microexons in PRUNE2 and PSAP, each containing 9 nt, which were altered within the specific domain during endothelial senescence. Conclusions These findings unveil the comprehensive transcriptome pathway and novel signaling regulated by RNA processing, including gene expression and splicing, in replicative endothelial senescence.Momoko OhoriYusuke NakayamaMari Ogasawara-ShimizuHiroyoshi ToyoshibaAtsushi NakanishiSamuel AparicioShinsuke ArakiBMCarticleReplicative senescenceHUVECAlternative splicingMicroexonMYCSIRT2BiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Replicative senescence HUVEC Alternative splicing Microexon MYC SIRT2 Biotechnology TP248.13-248.65 Genetics QH426-470
spellingShingle	Replicative senescence HUVEC Alternative splicing Microexon MYC SIRT2 Biotechnology TP248.13-248.65 Genetics QH426-470 Momoko Ohori Yusuke Nakayama Mari Ogasawara-Shimizu Hiroyoshi Toyoshiba Atsushi Nakanishi Samuel Aparicio Shinsuke Araki Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
description	Abstract Background Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in endothelial cell senescence is lacking. Results We thoroughly described the transcriptome landscape of replicative senescent human umbilical vein endothelial cells. Genes with high connectivity showing a monotonic expression increase or decrease with the culture period were defined as hub genes in the co-expression network. Computational network analysis of these genes led to the identification of canonical and non-canonical senescence pathways, such as E2F and SIRT2 signaling, which were down-regulated in lipid metabolism, and chromosome organization processes pathways. Additionally, we showed that endothelial cell senescence involves alternative splicing. Importantly, the first and last exon types of splicing, as observed in FLT1 and ACACA, were preferentially altered among the alternatively spliced genes during endothelial senescence. We further identified novel microexons in PRUNE2 and PSAP, each containing 9 nt, which were altered within the specific domain during endothelial senescence. Conclusions These findings unveil the comprehensive transcriptome pathway and novel signaling regulated by RNA processing, including gene expression and splicing, in replicative endothelial senescence.
format	article
author	Momoko Ohori Yusuke Nakayama Mari Ogasawara-Shimizu Hiroyoshi Toyoshiba Atsushi Nakanishi Samuel Aparicio Shinsuke Araki
author_facet	Momoko Ohori Yusuke Nakayama Mari Ogasawara-Shimizu Hiroyoshi Toyoshiba Atsushi Nakanishi Samuel Aparicio Shinsuke Araki
author_sort	Momoko Ohori
title	Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
title_short	Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
title_full	Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
title_fullStr	Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
title_full_unstemmed	Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
title_sort	gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8a3ccdb38a2246d8b51530ba78db631f
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Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence

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