Journal
STEM CELLS
Volume 39, Issue 12, Pages 1688-1700Publisher
OXFORD UNIV PRESS
DOI: 10.1002/stem.3453
Keywords
cell cycle genes; cellular reprogramming; cellular senescence; histone H3 methyltransferase; induced pluripotent stem cells
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Funding
- Ontario Graduate Scholarship (OGS)
- Cancer Research Society [19343]
- Canadian Institutes of Health Research [406811]
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Fully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells, which have great potential in disease modeling and regenerative medicine. However, this process has limitations due to the upregulation of antiproliferative genes, resulting in low efficiency. Our data reveals a unique cell cycle mechanism where mouse fibroblasts are able to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin-like protein SPY1, thus increasing reprogramming efficiency.
Fully 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 modeling and regenerative medicine. The process of remodeling has its limitations, including a very low efficiency due to the upregulation of many antiproliferative genes, including cyclin dependent kinase inhibitors CDKN1A and CDKN2A, 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.
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