Understanding the first steps in embryonic stem cell exit from the pluripotent state.

Understanding the first steps in embryonic stem cell exit from the pluripotent state.
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DOI:
10.1111/j.1537-2995.2011.03374.x
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发表时间:
2011-11
期刊:
影响因子:
2.9
通讯作者:
Marto JA
Marto JA
中科院分区:
医学3区
文献类型:
--
作者:
Luckey CJ;Lu Y;Marto JA

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We are interested in understanding how a given cell type, in response to external cues from its environment, makes the decision to differentiate. In the case of mouse embryonic stem cells (mESC), the key external factor that maintains their undifferentiated state is the cytokine leukemia inhibitory factor (LIF). LIF removal causes mESC to exit their pluripotent state and differentiate into more restricted precursors. Though LIF is known to activate multiple different phosphorylation cascades, the mechanisms by which its removal leads to mESC differentiation are not well understood. In order to identify the molecular events that occur upon LIF removal, we developed a set of novel experimental approaches that allowed identification and quantification of global phosphorylation changes that occur when mESC are deprived of LIF. Intriguingly, LIF removal results in the rapid phosphorylation of multiple proteins known to regulate the mESC self-renewal, though the specific function of these phosphorylations is unknown. Our data set the stage for future studies investigating the functional role of these phosphorylation events in mESC. We hypothesize that these unique post-translational modifications help drive the exit of mESC from the pluripotent state. These studies were greatly facilitated by the NBF, whose support in the crucial initiation phase of these studies was invaluable.
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