The Cyclin ‐Like Protein SPY1 overrides Reprogramming Induced Senescence Through EZH2 Mediated H3K27me3

Reprogramming of normal fibroblasts to induced pluripotent stem cells is characterized by low efficiency due to the upregulation of tumour suppressors and reprogramming induced senescence (RIS). Spy1 can be combined with classical pluripotency factors to override RIS through activation of EZH2 followed by an increase in trimethylation of histone H3 at the lysine 27 residue. AbstractFully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells. These cells share many characteristics of normal embryonic stem cells and have great promise in disease modelling and regenerative medicine. The process of remodelling has its limitations, including a very low efficiency due to the upregulation of many anti-proliferative genes, including cyclin dependent kinase inhibitorsCDKN1A andCDKN2A, which serve to protect the cell by inducing apoptotic and senescent programs. Our data reveals a unique cell cycle mechanism enabling mouse fibroblasts to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin-like protein SPY1. This data reveals that the SPY1 protein is required for reprogramming to a pluripotent state and is capable of increasing reprogramming efficiency.© AlphaMed Press 2021Significance StatementThis work reveals a mechanism used by normal fibroblasts to override reprogramming-induced senescence, thereby increasing the number of cells amenable to...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research