Proceedings of the National Academy of Sciences · 2012 · 87 citations · 16 references
Life SciencesCell BiologyDevelopmental BiologyCell DivisionCell ProliferationStem Cell BiologyCell Cycle ControlCell Cycle TransitionsCell-cycle PhasesCell-cycle RegulationEmbryonic Stem CellsStem Cell DifferentiationCell Cycle DynamicsCyclin-dependent Kinase ComplexesG1 Phase ControlG1 Phase Duration ControlG1 Phase ProgressionMouse Embryonic Stem CellsRetinoblastoma Family ProteinsStem Cell Cycle Regulation
In somatic cells, the length of the G1 phase of the cell cycle is tightly linked to differentiation, and its elongation can drive differentiation in many cases. Although it has been suggested that the situation is very similar in embryonic stem cells (ESCs), where a rapid cell cycle and a short G1 phase maintain the pluripotent state, evidence has been contradictory. Here we show that, in murine ESCs, elongation of the cell cycle and elongation of G1 are compatible with their pluripotent state. Multiple methods that lengthen the cell cycle and that target cyclin-dependent kinase, retinoblastoma protein, and E2F activity all fail to induce differentiation on their own or even to facilitate differentiation. The resistance of murine ESCs to differentiation induced by lengthening G1 and/or the cell cycle could allow for separate control of these events and provide new opportunities for investigation and application.
16
Distinct Roles for Cyclin-Dependent Kinases in Cell Cycle Control
Sander van den Heuvel, Ed Harlow · Science · 1993 · 1.1K citations
Cyril Berthet, Eiman Aleem, Vincenzo Coppola et al. · Current Biology · 2003 · 657 citations · Full text
Pluripotent cell division cycles are driven by ectopic Cdk2, cyclin A/E and E2F activities
Elaine Stead, Josephine White, Renate Faast et al. · Oncogene · 2002 · 388 citations · Full text