Transcriptome signature of cellular senescence

Abstract Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as...

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Veröffentlicht in:	Nucleic acids research Jg. 47; H. 14; S. 7294 - 7305
Hauptverfasser:	Casella, Gabriel, Munk, Rachel, Kim, Kyoung Mi, Piao, Yulan, De, Supriyo, Abdelmohsen, Kotb, Gorospe, Myriam
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England Oxford University Press 22.08.2019
Schlagworte:	Data Resources and Analyses
ISSN:	0305-1048, 1362-4962, 1362-4962
Online-Zugang:	Volltext
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Zusammenfassung:	Abstract Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage and β-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across eight diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 50 RNAs consistently elevated and 18 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some non-coding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy and the development of strategies to target senescent cells therapeutically.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0305-1048 1362-4962 1362-4962
DOI:	10.1093/nar/gkz555