Human Embryonic Stem Cells Are Pre-Mitotically Committed to Self-Renewal and Acquire a Lengthened G1 Phase Upon Lineage Programming

Self-renewal of human embryonic stem (hES) cells proceeds by a unique abbreviated cell cycle with a shortened G I phase and distinctions in molecular cell cycle regulatory parameters. In this study, we show that early lineage-commitment of pluripotent hES cells modifies cell cycle kinetics. Human ES cells acquire a lengthened GI within 72 h after lineage-programming is initiated, as reflected by loss of the pluripotency factor Oct4 and alterations in nuclear morphology. In hES cells that maintain the pristine pluripotent state, we find that autocrine mechanisms contribute to sustaining the abbreviated cell cycle. Our data show that naive and mitotically synchronized pluripotent hES cells are competent to initiate two consecutive S phases in the absence of external growth factors. We conclude that short-term self-renewal of pluripotent hES cells occurs autonomously, in part due to secreted factors, and that pluripotency is functionally linked to the abbreviated hES cell cycle. J. Cell. Physiol. 222: 103-110, 2010. (C) 2009 Wiley-Liss, Inc.