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Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

BACKGROUND: Cellular senescence is induced either internally, for example by replication exhaustion and cell division, or externally, for example by irradiation. In both cases, cellular damages accumulate which, if not successfully repaired, can result in senescence induction. Recently, we determine...

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Autores principales: Marthandan, Shiva, Menzel, Uwe, Priebe, Steffen, Groth, Marco, Guthke, Reinhard, Platzer, Matthias, Hemmerich, Peter, Kaether, Christoph, Diekmann, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963952/
https://www.ncbi.nlm.nih.gov/pubmed/27464526
http://dx.doi.org/10.1186/s40659-016-0095-2
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author Marthandan, Shiva
Menzel, Uwe
Priebe, Steffen
Groth, Marco
Guthke, Reinhard
Platzer, Matthias
Hemmerich, Peter
Kaether, Christoph
Diekmann, Stephan
author_facet Marthandan, Shiva
Menzel, Uwe
Priebe, Steffen
Groth, Marco
Guthke, Reinhard
Platzer, Matthias
Hemmerich, Peter
Kaether, Christoph
Diekmann, Stephan
author_sort Marthandan, Shiva
collection PubMed
description BACKGROUND: Cellular senescence is induced either internally, for example by replication exhaustion and cell division, or externally, for example by irradiation. In both cases, cellular damages accumulate which, if not successfully repaired, can result in senescence induction. Recently, we determined the transcriptional changes combined with the transition into replicative senescence in primary human fibroblast strains. Here, by γ-irradiation we induced premature cellular senescence in the fibroblast cell strains (HFF and MRC-5) and determined the corresponding transcriptional changes by high-throughput RNA sequencing. RESULTS: Comparing the transcriptomes, we found a high degree of similarity in differential gene expression in replicative as well as in irradiation induced senescence for both cell strains suggesting, in each cell strain, a common cellular response to error accumulation. On the functional pathway level, “Cell cycle” was the only pathway commonly down-regulated in replicative and irradiation-induced senescence in both fibroblast strains, confirming the tight link between DNA repair and cell cycle regulation. However, “DNA repair” and “replication” pathways were down-regulated more strongly in fibroblasts undergoing replicative exhaustion. We also retrieved genes and pathways in each of the cell strains specific for irradiation induced senescence. CONCLUSION: We found the pathways associated with “DNA repair” and “replication” less stringently regulated in irradiation induced compared to replicative senescence. The strong regulation of these pathways in replicative senescence highlights the importance of replication errors for its induction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40659-016-0095-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-49639522016-07-29 Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence Marthandan, Shiva Menzel, Uwe Priebe, Steffen Groth, Marco Guthke, Reinhard Platzer, Matthias Hemmerich, Peter Kaether, Christoph Diekmann, Stephan Biol Res Research Article BACKGROUND: Cellular senescence is induced either internally, for example by replication exhaustion and cell division, or externally, for example by irradiation. In both cases, cellular damages accumulate which, if not successfully repaired, can result in senescence induction. Recently, we determined the transcriptional changes combined with the transition into replicative senescence in primary human fibroblast strains. Here, by γ-irradiation we induced premature cellular senescence in the fibroblast cell strains (HFF and MRC-5) and determined the corresponding transcriptional changes by high-throughput RNA sequencing. RESULTS: Comparing the transcriptomes, we found a high degree of similarity in differential gene expression in replicative as well as in irradiation induced senescence for both cell strains suggesting, in each cell strain, a common cellular response to error accumulation. On the functional pathway level, “Cell cycle” was the only pathway commonly down-regulated in replicative and irradiation-induced senescence in both fibroblast strains, confirming the tight link between DNA repair and cell cycle regulation. However, “DNA repair” and “replication” pathways were down-regulated more strongly in fibroblasts undergoing replicative exhaustion. We also retrieved genes and pathways in each of the cell strains specific for irradiation induced senescence. CONCLUSION: We found the pathways associated with “DNA repair” and “replication” less stringently regulated in irradiation induced compared to replicative senescence. The strong regulation of these pathways in replicative senescence highlights the importance of replication errors for its induction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40659-016-0095-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-28 /pmc/articles/PMC4963952/ /pubmed/27464526 http://dx.doi.org/10.1186/s40659-016-0095-2 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Marthandan, Shiva
Menzel, Uwe
Priebe, Steffen
Groth, Marco
Guthke, Reinhard
Platzer, Matthias
Hemmerich, Peter
Kaether, Christoph
Diekmann, Stephan
Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
title Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
title_full Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
title_fullStr Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
title_full_unstemmed Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
title_short Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
title_sort conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963952/
https://www.ncbi.nlm.nih.gov/pubmed/27464526
http://dx.doi.org/10.1186/s40659-016-0095-2
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