Notch signalling is essential for secondary senescence and confers a facultative senescence end point in primary cells
Session type: Poster / e-Poster / Silent Theatre session
Cellular senescence is a response to a variety of stresses, acting as a tumour suppressor mechanism, but also contributing to ageing. One of the factors mediating positive and negative effects of cellular senescence is the senescence-associated secretory phenotype (SASP). SASP factors can act in an autocrine fashion or in a paracrine manner, inducing secondary senescence in surrounding cells and tissues. The interplay between triggers of primary and secondary senescence is likely to result in complex and heterogeneous cell populations. Capturing this heterogeneity and mapping differences between secondary and primary senescent cells will answer questions regarding functional diversification of cells and varying degrees of cell cycle arrest.
Here we use single-cell transcriptomics in co-culture systems to decipher the heterogeneity within stress-induced senescent populations.
We identify two facultative transcriptional endpoints for primary senescence, one driven by RasV12 activation and one driven by Notch signalling. We also find secondary senescent cells to carry a pronounced Notch signature, distinct from paracrine senescence, in vivo and in vitro, highlighting non-canonical ways of secondary senescence induction. We provide further evidence for a functional role of Notch in secondary senescence, implicating Notch as the main driver of secondary senescence.
Notch signalling is essential for secondary senescence and drives a facultative endpoint in primary senescence.