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 G1 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 G1 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 naïve 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.
Becker
Klaus A
KA
Department of Cell Biology, Cancer Center and Center for Stem Cell Biology and Regenerative Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Stein
Janet L
JL
Lian
Jane B
JB
van Wijnen
Andre J
AJ
Stein
Gary S
GS
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D004247:DNA