共查询到20条相似文献,搜索用时 609 毫秒
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Ganeshkumar Rajendran Debasree Dutta James Hong Arindam Paul Biswarup Saha Biraj Mahato Soma Ray Pratik Home Avishek Ganguly Mark L. Weiss Soumen Paul 《The Journal of biological chemistry》2013,288(34):24351-24362
Embryonic stem cell (ESC) pluripotency is orchestrated by distinct signaling pathways that are often targeted to maintain ESC self-renewal or their differentiation to other lineages. We showed earlier that inhibition of PKC signaling maintains pluripotency in mouse ESCs. Therefore, in this study, we investigated the importance of protein kinase C signaling in the context of rat ESC (rESC) pluripotency. Here we show that inhibition of PKC signaling is an efficient strategy to establish and maintain pluripotent rESCs and to facilitate reprogramming of rat embryonic fibroblasts to rat induced pluripotent stem cells. The complete developmental potential of rESCs was confirmed with viable chimeras and germ line transmission. Our molecular analyses indicated that inhibition of a PKCζ-NF-κB-microRNA-21/microRNA-29 regulatory axis contributes to the maintenance of rESC self-renewal. In addition, PKC inhibition maintains ESC-specific epigenetic modifications at the chromatin domains of pluripotency genes and, thereby, maintains their expression. Our results indicate a conserved function of PKC signaling in balancing self-renewal versus differentiation of both mouse and rat ESCs and indicate that targeting PKC signaling might be an efficient strategy to establish ESCs from other mammalian species. 相似文献
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Graveley BR 《Cell》2011,147(1):22-24
In this issue of Cell, Gabut and colleagues (2011) identify a new splice variant of FOXP1 that directly regulates the expression of pluripotency genes. It endows human embryonic stem cells with their pluripotent nature and is required for the reprogramming of somatic cells to induced pluripotent stem cells. 相似文献
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Krüppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs 总被引:1,自引:0,他引:1
Ema M Mori D Niwa H Hasegawa Y Yamanaka Y Hitoshi S Mimura J Kawabe Y Hosoya T Morita M Shimosato D Uchida K Suzuki N Yanagisawa J Sogawa K Rossant J Yamamoto M Takahashi S Fujii-Kuriyama Y 《Cell Stem Cell》2008,3(5):555-567
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Calcineurin-NFAT signaling critically regulates early lineage specification in mouse embryonic stem cells and embryos 总被引:1,自引:0,他引:1
Self-renewal and pluripotency are hallmarks of embryonic stem cells (ESCs). However, the signaling pathways that trigger their transition from self-renewal to differentiation remain elusive. Here, we report that calcineurin-NFAT signaling is both necessary and sufficient to switch ESCs from an undifferentiated state to lineage-specific cells and that the inhibition of this pathway can maintain long-term ESC self-renewal independent of leukemia inhibitory factor. Mechanistically, this pathway converges with the Erk1/2 pathway to regulate Src expression and promote the epithelial-mesenchymal transition (EMT), a process required for lineage specification in response to differentiation stimuli. Furthermore, calcineurin-NFAT signaling is activated when the earliest differentiation event occurs in mouse embryos, and its inhibition disrupts extraembryonic lineage development. Collectively, our results demonstrate that the NFAT and Erk1/2 cascades form a signaling switch for early lineage segregation in mouse ESCs and provide significant insights into the regulation of the balance between ESC self-renewal and early lineage specification. 相似文献
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Yajun Liu De Cheng Zhenzhen Li Xing Gao Huayan Wang 《Genetics and molecular biology》2012,35(3):693-700
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