Deconstructing replicative senescence heterogeneity of human mesenchymal stem cells at single cell resolution reveals therapeutically targetable senescent cell sub-populations

Cellular senescence is characterised by a state of permanent cell cycle arrest. While cellular senescence is a recognised driver of organismal ageing, the extent of heterogeneity within and between different senescent cell populations remains largely unclear. Here we combined cell biological and single cell RNA-sequencing approaches to investigate heterogeneity of replicative senescence in human ESC-derived mesenchymal stem cells (esMSCs) as MSCs are the cell type of choice for the majority of current stem cell herapies and senescence of MSC is a recognized driver of organismal ageing. We identified three senescing esMSC subpopulations and their associated maker genes, allowing us to identify potential drug targets that may delay the emergence of senescent MSCs in vitro and perhaps in vivo in the future. Overall design: Mesenchymal stem cells undergoing replicative senescence. Three timepoints and three biological replicates in each timepoint. Over all 9 samples.