期刊论文详细信息
Biological research: BR
Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
Shiva Marthandan1  Matthias Platzer1  Stephan Diekmann1  Uwe Menzel2  Marco Groth2  Peter Hemmerich2  Christoph Kaether3  Reinhard Guthke3  Steffen Priebe3 
[1] Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Jena, Germany;Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute e.V. (HKI), Jena, Germany
关键词: Senescence;    Fibroblasts;    γ-irradiation;    Aging;    Transcriptome analysis;    DNA repair;   
DOI  :  10.1186/s40659-016-0095-2
学科分类:生物科学(综合)
来源: BioMed Central
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【 摘 要 】

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. 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. 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.

【 授权许可】

CC BY   

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