Cell Cycle Control of Embryonic Stem Cells

Abstract

Embryonic stem cells have the capacity for unlimited proliferation while retaining their potential to differentiate into a wide variety of cell types. Murine, primate and human embryonic stem cells (ESCs) exhibit a very unusual cell cycle structure, characterized by a short G1 phase and a high proportion of cells in S-phase. In the case of mESCs, this is associated with a unique mechanism of cell cycle regulation, underpinned by the precocious activity of cyclin dependent protein kinase (Cdk) activities. As ES cells differentiate, their cell cycle structure changes dramatically so as to incorporate a significantly longer G1 phase and their mechanism of cell cycle regulation changes to that typically seen in other mammalian cells. The unique cell cycle structure and mechanism of cell cycle control indicates that the cell cycle machinery plays a role in establishment or maintenance of the stem cell state. This idea is supported by the frequent involvement of cell cycle regulatory molecules in cell immortalization.