Transcriptome signature of cellular senescence. Issue 14 (28th June 2019)

• Record Type: Journal Article
• Authors: Casella, Gabriel; Munk, Rachel; Kim, Kyoung Mi; Piao, Yulan; De, Supriyo; Abdelmohsen, Kotb; Gorospe, Myriam
• Is Part Of: Nucleic acids research. Volume 47:Issue 14(2019)
• Page Start: 7294
• Page End: 7305
• Publication Date: 2019-06-28
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkz555
• Languages: English
• ISSNs: 0305-1048

Abstract

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 HRAS G12V . 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.