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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    • "AURKB has also been associated with TMZ susceptibility[23]and aggressive outcomes of glioblastomas[24]. CDK1 is also known to play regulatory roles in the self-renewal of mouse embryonic stem cells[25]as well as for cell survival of glioblastoma[26]. These findings may support that the selective targeting of these genes for G1 recurrent tumors might be beneficial in the clinic. "
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    ABSTRACT: Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6) in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprograming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.
    Full-text · Article · Oct 2015 · PLoS ONE
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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).
    Full-text · Article · Oct 2012 · FEBS letters
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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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    Full-text · Article · Dec 2011
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