Demaria Group: Unmasking Transcriptional Heterogeneity in Senescent Cells

Scientists of the European Research Institute for the Biology of Ageing (ERIBA) unravelled the complexity of gene regulation during cellular senescence. The study, carried out in the group of Marco Demaria and in the and led by Alejandra Hernandez-Segura, was published in the journal Current Biology .

Cellular senescence is a complex state of irreversibe growth arrest. Senescent cells participate in a variety of physiological and pathological conditions, including tumor suppression, embryonic development, tissue repair, and organismal aging. Senescent cells are characterized by the transcriptional induction of a number of non-exclusive markers such as senescence-associated β-galactosidase (SA-βgal), the cell cycle inhibitors p16 and p21, and many bio-active factors (the senescence-associated secretory phenotype, or SASP). However, the transcriptional activation of these markers during senescence is highly variable, and methods for clearly identifying senescent cells are lacking. In this study, the Demaria team with the help of colleagues from the ERIBA and the Buck Institute for Research on Aging (Novato CA, USA) characterized the heterogeneity of the senescence program using numerous whole-transcriptome datasets generated by the lab or publicly available.

They identified transcriptome signatures associated with specific senescence-inducing stresses or senescent cell types and validate genes that are commonly differentially regulated. Moreover, they showed that the senescent phenotype is dynamic, changing at varying intervals after senescence induction. These novel transcriptome signatures may help to discriminate among diverse senescence programs, but also as the basis for developing drugs specifically interfering with sub-types of senescent cells