Cargando…
Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
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 endothel...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641155/ https://www.ncbi.nlm.nih.gov/pubmed/34856941 http://dx.doi.org/10.1186/s12864-021-08185-x |
_version_ | 1784609451116855296 |
---|---|
author | Ohori, Momoko Nakayama, Yusuke Ogasawara-Shimizu, Mari Toyoshiba, Hiroyoshi Nakanishi, Atsushi Aparicio, Samuel Araki, Shinsuke |
author_facet | Ohori, Momoko Nakayama, Yusuke Ogasawara-Shimizu, Mari Toyoshiba, Hiroyoshi Nakanishi, Atsushi Aparicio, Samuel Araki, Shinsuke |
author_sort | Ohori, Momoko |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-08185-x. |
format | Online Article Text |
id | pubmed-8641155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86411552021-12-03 Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence Ohori, Momoko Nakayama, Yusuke Ogasawara-Shimizu, Mari Toyoshiba, Hiroyoshi Nakanishi, Atsushi Aparicio, Samuel Araki, Shinsuke BMC Genomics Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-08185-x. BioMed Central 2021-12-02 /pmc/articles/PMC8641155/ /pubmed/34856941 http://dx.doi.org/10.1186/s12864-021-08185-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ohori, Momoko Nakayama, Yusuke Ogasawara-Shimizu, Mari Toyoshiba, Hiroyoshi Nakanishi, Atsushi Aparicio, Samuel Araki, Shinsuke Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence |
title | 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_short | 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 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641155/ https://www.ncbi.nlm.nih.gov/pubmed/34856941 http://dx.doi.org/10.1186/s12864-021-08185-x |
work_keys_str_mv | AT ohorimomoko generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence AT nakayamayusuke generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence AT ogasawarashimizumari generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence AT toyoshibahiroyoshi generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence AT nakanishiatsushi generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence AT apariciosamuel generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence AT arakishinsuke generegulatorynetworkanalysisdefinestranscriptomelandscapewithalternativesplicingofhumanumbilicalveinendothelialcellsduringreplicativesenescence |