Cdk1 is required for the self-renewal of mouse embryonic stem cells

College of Life Sciences, Capital Normal University, Beijing, China.
Journal of Cellular Biochemistry (Impact Factor: 3.26). 03/2011; 112(3). DOI: 10.1002/jcb.23010
Source: PubMed


Cyclin-dependent kinase 1 (Cdk1) is indispensible for the early development of the embryo. However, its role in maintaining the undifferentiated state of the embryonic stem (ES) cells remains unknown. In this study, we dissected the function of Cdk1 in mouse ES cells by RNA-interference and gene expression analyses. Cdk1 expression is tightly correlated with the undifferentiated state of the ES cells. Upon differentiation, Cdk1 expression reduced drastically. Cdk1 knock-down by RNA interference resulted in the loss of proliferation and colony formation potential of the ES cells. Consequentially, expression of self-renewal genes was reduced while differentiation markers such as Cdx2 were induced. Our results suggest a role for Cdk1 in maintaining the unique undifferentiated and self-renewing state of the mouse ES cells. © 2010 Wiley-Liss, Inc.

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Available from: Wei Xiao, Dec 18, 2013
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    • "This finding is consistent with previous observation that Cdk1-depleted ES cells exhibit a dramatic increase in Cdx2 transcript [16]. As shown by our previous study, Cdx2 is one of the highlighted genes whose expression shows significant changed [16]. For example , Mesoendoderm marker Msx1 and ectoderm Fgf5 are also greatly up-regulated upon Cdk1 depletion. "
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    ABSTRACT: Cdk1 plays an important role in undifferentiated ES cells, but the underlying mechanism remains unclear. This study explores how Cdk1 collaborates with Oct4 to inhibit differentiation in mouse ES cells. We show a direct interaction between Cdk1 and Oct4, whereas other Cdk members, including Cdk2 and Cdk4, fail to associate with Oct4. By immunocytochemistry we show that Cdk1 and Oct4 co-localize in ES cells. The biological function of the Cdk1-Oct4 complex was also addressed. We found that Cdk1 enhances the binding of Oct4 on the trophectoderm marker Cdx2 and promotes Cdx2 repression. This regulation is independent of cyclins and of the kinase activity of Cdk1. Our study explains how Cdk1 and Oct4 interplay to inhibit ES cell differentiation into trophectoderm and thereby maintain stemness. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: Cdk1physically interactswithOct4byanti tag coimmunoprecipitation(View interaction) Oct4bindstoSOX-2bypull down(View interaction) Cdk1physically interactswithOct4andcyclin-B1byanti bait coimmunoprecipitation(View interaction) Oct4bindstoCdk1bypull down(View interaction) Cdk1andOct4colocalizebyfluorescence microscopy(View interaction) Oct4physically interactswithSox2byanti bait coimmunoprecipitation(View interaction).
    FEBS letters 10/2012; 586(23). DOI:10.1016/j.febslet.2012.10.030 · 3.17 Impact Factor
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    • "Cyclin-dependent kinase 1 (Cdk1) is indispensable for the early development of the embryos. Cdk1 expression is tightly correlated with the undifferentiated state of ES cells by maintaining the unique undifferentiated and self-renewing state of mouse ES cells [55], whereas Cdk1 has a crucial role in orchestrating a fine balance between cellular proliferation, cell death and DNA repair in hESCs [56]. Recently, it was shown that the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the expression and activator functionality of Zfp521 [57]. "
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    ABSTRACT: It is a general concern that the success of regenerative medicine-based applications is based on the ability to recapitulate the molecular events that allow stem cells to repair the damaged tissue/organ. To this end biomaterials are designed to display properties that, in a precise and physiological-like fashion, could drive stem cell fate both in vitro and in vivo. The rationale is that stem cells are highly sensitive to forces and that they may convert mechanical stimuli into a chemical response. In this review, we describe novelties on stem cells and biomaterials interactions with more focus on the implication of the mechanical stimulation named mechanotransduction.
    12/2011; 2(2):67-87. DOI:10.3390/jfb2020067
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    • "In addition to transcription-related activities, Oct4 also affiliates with proteins involved in cell cycle regulation. Cdk1 has previously been established in an Oct4 interaction network [28] and is critical for the self-renewal of ES cells [47]. Because of the unique cell cycle phasing of ES cells with a short G1/S phase that promotes rapid proliferation [48-50], the coupling of Oct4 activity with cell cycle kinases such as Cdk1 may be necessary for rapid and direct coordination of genomic activity with cell division, failing which apoptosis may occur, as shown by ES cells depleted of Cdk1 [47]. "
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    ABSTRACT: Octamer-binding transcription factor 4 (Oct4) is a master regulator of early mammalian development. Its expression begins from the oocyte stage, becomes restricted to the inner cell mass of the blastocyst and eventually remains only in primordial germ cells. Unearthing the interactions of Oct4 would provide insight into how this transcription factor is central to cell fate and stem cell pluripotency. In the present study, affinity-tagged endogenous Oct4 cell lines were established via homologous recombination gene targeting in embryonic stem (ES) cells to express tagged Oct4. This allows tagged Oct4 to be expressed without altering the total Oct4 levels from their physiological levels. Modified ES cells remained pluripotent. However, when modified ES cells were tested for their functionality, cells with a large tag failed to produce viable homozygous mice. Use of a smaller tag resulted in mice with normal development, viability and fertility. This indicated that the choice of tags can affect the performance of Oct4. Also, different tags produce a different repertoire of Oct4 interactors. Using a total of four different tags, we found 33 potential Oct4 interactors, of which 30 are novel. In addition to transcriptional regulation, the molecular function associated with these Oct4-associated proteins includes various other catalytic activities, suggesting that, aside from chromosome remodeling and transcriptional regulation, Oct4 function extends more widely to other essential cellular mechanisms. Our findings show that multiple purification approaches are needed to uncover a comprehensive Oct4 protein interaction network.
    Stem Cell Research & Therapy 05/2011; 2(3):26. DOI:10.1186/scrt67 · 3.37 Impact Factor
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