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Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their trans...

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Autores principales: Marthandan, S., Baumgart, M., Priebe, S., Groth, M., Schaer, J., Kaether, C., Guthke, R., Cellerino, A., Platzer, M., Diekmann, S., Hemmerich, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854426/
https://www.ncbi.nlm.nih.gov/pubmed/27140416
http://dx.doi.org/10.1371/journal.pone.0154531
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author Marthandan, S.
Baumgart, M.
Priebe, S.
Groth, M.
Schaer, J.
Kaether, C.
Guthke, R.
Cellerino, A.
Platzer, M.
Diekmann, S.
Hemmerich, P.
author_facet Marthandan, S.
Baumgart, M.
Priebe, S.
Groth, M.
Schaer, J.
Kaether, C.
Guthke, R.
Cellerino, A.
Platzer, M.
Diekmann, S.
Hemmerich, P.
author_sort Marthandan, S.
collection PubMed
description Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.
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spelling pubmed-48544262016-05-07 Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq Marthandan, S. Baumgart, M. Priebe, S. Groth, M. Schaer, J. Kaether, C. Guthke, R. Cellerino, A. Platzer, M. Diekmann, S. Hemmerich, P. PLoS One Research Article Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains. Public Library of Science 2016-05-03 /pmc/articles/PMC4854426/ /pubmed/27140416 http://dx.doi.org/10.1371/journal.pone.0154531 Text en © 2016 Marthandan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Marthandan, S.
Baumgart, M.
Priebe, S.
Groth, M.
Schaer, J.
Kaether, C.
Guthke, R.
Cellerino, A.
Platzer, M.
Diekmann, S.
Hemmerich, P.
Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq
title Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq
title_full Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq
title_fullStr Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq
title_full_unstemmed Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq
title_short Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq
title_sort conserved senescence associated genes and pathways in primary human fibroblasts detected by rna-seq
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854426/
https://www.ncbi.nlm.nih.gov/pubmed/27140416
http://dx.doi.org/10.1371/journal.pone.0154531
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