Role of cyclins and cyclin-dependent kinases in pluripotent stem cells and their potential as a therapeutic target

•The cell cycle machinery has a prominent role in stem cell pluripotency and self-renewal.•Cyclin-dependent protein kinases and their effectors have key roles in control of cell fate decisions.•The availability of highly-specific inhibitors for components of the cell cycle machinery opens up opportunities for control of stem cell characteristics, reprogramming and disease treatment. Over the last 15 years connections between cell cycle control, maintenance of pluripotency, and control of cell fate decisions have been firmly established. With the emergence of powerful tools, such as highly-specific small molecule inhibitors for cyclin-dependent protein kinase (CDK) activity and single-cell imaging technologies, the mechanistic links between cyclins, CDKs and regulation in PSCs in mechanistic detail has been made possible. In this review, we discuss new developments that mechanistically link the CDK regulatory network to control of cell fate decisions, including maintenance of the pluripotent state. Overall, these findings have potential to impact the translational applications of stem cells in regenerative medicine, drug discovery and cancer treatment.