title: A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency.
abstract: A short G1 phase is a characteristic feature of mouse embryonic stem cells (ESCs). To determine if there is a causal relationship between G1 phase restriction and pluripotency, we made use of the Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) reporter system to FACS-sort ESCs in the different cell cycle phases. Hence, the G1 phase cells appeared to be more susceptible to differentiation, particularly when ESCs self-renewed in the naïve state of pluripotency. Transitions from ground to naïve, then from naïve to primed states of pluripotency were associated with increased durations of the G1 phase, and cyclin E-mediated alteration of the G1/S transition altered the balance between self-renewal and differentiation. LIF withdrawal resulted in a lengthening of the G1 phase in naïve ESCs, which occurred prior to the appearance of early lineage-specific markers, and could be reversed upon LIF supplementation. We concluded that the short G1 phase observed in murine ESCs was a determinant of naïve pluripotency and was partially under the control of LIF signaling.
authors.affiliation: Stem Cell and Brain Research Institute, Bron, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Coronado
authors.forename: Murielle
authors.initials: M
authors.lastname: Godet
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bourillot
authors.forename: Yann
authors.initials: Y
authors.lastname: Tapponnier
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bernat
authors.forename: Maxime
authors.initials: M
authors.lastname: Petit
authors.forename: Marielle
authors.initials: M
authors.lastname: Afanassieff
authors.forename: Suzy
authors.initials: S
authors.lastname: Markossian
authors.forename: Anna
authors.initials: A
authors.lastname: Malashicheva
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacone
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anastassiadis
authors.forename: Pierre
authors.initials: P
authors.lastname: Savatier
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019927:Cyclin E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D018613:Microscopy, Confocal; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D054875:Ubiquitination
chemical_list: D019927:Cyclin E; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D034741:RNA, Small Interfering