Cell Cycle Features of Primate Embryonic Stem Cells

Anne-Catherine Fluckiger^a^,b, Guillaume Marcy^a^,b, Mélanie Marchand^a^,b, Didier Négre^c^,d^,e, François-Loïc Cosset^c^,d^,e, Shoukhrat Mitalipov^f, Don Wolf^f, Pierre Savatier^a^,b^,g, Colette Dehay^a^,b^,g

^a Institut National de la Santé et de la Recherche Médicale (INSERM), U371, Cerveau et Vision, Department of Stem Cells and Cortical Development, Bron, France;
^b Université Claude Bernard Lyon I, IFR19 Institut Fédératif des Neurosciences, Bron, France;
^c INSERM, U412, Lyon, France;
^d Ecole Normale Supérieure de Lyon, Lyon, France;
^e Université Claude Bernard Lyon I, IFR128 BioSciences Lyon-Gerland, Lyon, France;
^f Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA;
^g INSERM, U371, PrimaStem, Bron, France

Key Words. Rhesus embryonic stem cells • Cell cycle • Stemness

Correspondence: Pierre Savatier, Ph.D., INSERM, U371, Cerveau et Vision, Department of Stem Cells and Cortical Development, 18 avenue Doyen Lépine, 69500 Bron, France. Telephone: +33 4 72 91 34 42; Fax: +33 4 72 91 34 61; e-mail: savatier{at}lyon.inserm.fr

Received April 27, 2005; accepted for publication October 12, 2005.
Using flow cytometry measurements combined with quantitativeanalysis of cell cycle kinetics, we show that rhesus monkeyembryonic stem cells (ESCs) are characterized by an extremelyrapid transit through the G₁ phase, which accounts for 15% ofthe total cell cycle duration. Monkey ESCs exhibit a non-phasicexpression of cyclin E, which is detected during all phasesof the cell cycle, and do not growth-arrest in G₁ after ${gamma}$ -irradiation,reflecting the absence of a G₁ checkpoint. Serum deprivationor pharmacological inhibition of mitogen-activated protein kinasekinase (MEK) did not result in any alteration in the cell cycledistribution, indicating that ESC growth does not rely on mitogenicsignals transduced by the Ras/Raf/MEK pathway. Taken together,these data indicate that rhesus monkey ESCs, like their murinecounterparts, exhibit unusual cell cycle features in which cellcycle control mechanisms operating during the G₁ phase are reducedor absent.