A short G1 phase is an intrinsic determinant of na?ve embryonic stem cell pluripotency

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• 作者：Diana Coronado^a ; ^b ; ^c ; Murielle Godet^a ; ^b ; ^c ; ^e ; Pierre-Yves Bourillot^a ; ^b ; ^c ; ^d ; Yann Tapponnier^a ; ^b ; ^c ; Agnieszka Bernat^a ; ^b ; ^c ; ¹ ; Maxime Petit^a ; ^b ; ^c ; Marielle Afanassieff^a ; ^b ; ^c ; ^e ; Suzy Markossian^a ; ^b ; ^c ; ^e ; Anna Malashicheva^a ; ^b ; ^c ; ² ; Roberto Iacone^f ; ³ ; Konstantinos Anastassiadis^f ; Pierre Savatier^a ; ^b ; ^c ; ^d ; ^e ; ^{pierre.savatier@inserm.fr}
• 关键词：FUCCI ; Fluorescence Ubiquitination Cell Cycle Indicator
• 刊名：Stem Cell Research
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：10
• 期：1
• 页码：118-131
• 全文大小：2069 K

文摘

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 na?ve state of pluripotency. Transitions from ground to na?ve, then from na?ve 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 na?ve 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 na?ve pluripotency and was partially under the control of LIF signaling.