Transcriptome signature of cellular senescence
Casella G, Munk R, Kim KM, Piao Y, De S, Abdelmohsen K, Gorospe M. Transcriptome signature of cellular senescence. Nucleic Acids Res. 2019 Aug 22;47(14):7294-7305. doi: 10.1093/nar/gkz555. Erratum in: Nucleic Acids Res. 2019 Dec 2;47(21):11476. PMID: 31251810; PMCID: PMC6698740.
Cellular senescence has a number of characteristics including DNA damage, induction of the p53/CDKN1A (p21) and CDKN2A (p16)/pRB pathways, senescence-associated β-galactosidase activity, cytoskeletal alterations, the formation of senescence-associated heterochromatin foci, and the SASP. However, these markers of senescence are not universal and are not a good way to ensure that a cell is senescent.
This study used universally expressed transcripts from different senescent cell models and, using RNA-seq, found RNAs that could be used to identify senescent cells.
The main differences in RNA expression depended on the cell type of origin, and not on the senescence induction method which supports the idea that senescence is not a single phenotypic state.
The RNA-seq analysis revealed 50 elevated and 18 reduced transcripts between the senescent and non-senescent cells, some of which were consistent between all senescence models and were more uniform than the p21 and p16 markers.
Examining the 68 transcripts shared between the senescent types, a PCA showed that senescence state gave the clearest separation between the cell types. An ML models using LASSO showed that 5 transcripts, SLCO2B1, CLSTN2, PTCHD4 mRNAs and LINCO2154 and PURPL lncRNAs, were the minimum needed to distinguish senescent cells. PURPL was one of the most highly and consistently elevated transcripts and is controlled by the transcription factor p53, which is elevated in senescent cells. It may contribute to the survival of senescent cells as it does in tumors.