共查询到20条相似文献,搜索用时 31 毫秒
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Embryonic stem cell markers expression in cancers 总被引:1,自引:0,他引:1
Matthieu Schoenhals John De Vos Dirk Hose Bernard Klein 《Biochemical and biophysical research communications》2009,383(2):157-162
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Stem cell pluripotency and transcription factor Oct4 总被引:10,自引:1,他引:9
GUANG JIN PAN ZENG YI CHANG HANS R. SCHOLER DUANQING PEI Departments of Pharmacology Biological Sciences & Biotechnology Schools of Sciences Medicine Tsinghua University Beijing China Center for Animal Transgenesis Germ Cell Research School of Veterinary Medicine Department of Animal Biology University of Pennsylvania New Bolton Center West Street Road Kennett Square PA USA Department of Pharmacology University of Minnesota Minneapolis MN USA 《Cell research》2002,(Z2)
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Stem cell pluripotency and transcription factor Oct4 总被引:4,自引:0,他引:4
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SP Liu HJ Harn YJ Chien CH Chang CY Hsu RH Fu YC Huang SY Chen WC Shyu SZ Lin 《PloS one》2012,7(9):e44024
In 2006, induced pluripotent stem (iPS) cells were generated from somatic cells by introducing Oct4, Sox2, c-Myc and Klf4. The original process was inefficient; maintaining the pluripotency of embryonic stem (ES) and iPS cell cultures required an expensive reagent-leukemia induced factor (LIF). Our goal is to find a pure compound that not only maintains ES and iPS cell pluripotency, but also increases iPS cell generation efficiency. From 15 candidate compounds we determined that 10 μg/ml n-Butylidenephthalide (BP), an Angelica sinensis extract, triggers the up-regulation of Oct4 and Sox2 gene expression levels in MEF cells. We used ES and iPS cells treated with different concentrations of BP to test its usefulness for maintaining stem cell pluripotency. Results indicate higher expression levels of several stem cell markers in BP-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryoid body formation and differentiation results confirm that BP containing medium culture was capable of maintaining ES cell pluripotency after six time passage. Microarray analysis data identified PPAR, ECM, and Jak-Stat signaling as the top three deregulated pathways. We subsequently determined that phosphorylated Jak2 and phosphorylated Stat3 protein levels increased following BP treatment and suppressed with the Jak2 inhibitor, AG490. The gene expression levels of cytokines associated with the Jak2-Stat3 pathway were also up-regulated. Last, we used pou5f1-GFP MEF cells to test iPS generation efficiency following BP treatment. Our data demonstrate the ability of BP to maintain stem cell pluripotency via the Jak2-Stat3 pathway by inducing cytokine expression levels, at the same time improving iPS generation efficiency. 相似文献
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Kehler J Tolkunova E Koschorz B Pesce M Gentile L Boiani M Lomelí H Nagy A McLaughlin KJ Schöler HR Tomilin A 《EMBO reports》2004,5(11):1078-1083
Previous studies have shown that Oct4 has an essential role in maintaining pluripotency of cells of the inner cell mass (ICM) and embryonic stem cells. However, Oct4 null homozygous embryos die around the time of implantation, thus precluding further analysis of gene function during development. We have used the conditional Cre/loxP gene targeting strategy to assess Oct4 function in primordial germ cells (PGCs). Loss of Oct4 function leads to apoptosis of PGCs rather than to differentiation into a trophectodermal lineage, as has been described for Oct4-deficient ICM cells. These new results suggest a previously unknown function of Oct4 in maintaining viability of mammalian germline. 相似文献
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Hammachi F Morrison GM Sharov AA Livigni A Narayan S Papapetrou EP O'Malley J Kaji K Ko MS Ptashne M Brickman JM 《Cell reports》2012,1(2):99-109
Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show that fusion proteins containing the coding sequence of Oct4 or Xlpou91 (the Xenopus homolog of Oct4) fused to activating regions, but not those fused to repressing regions, behave as Oct4, suppressing differentiation and promoting maintenance of undifferentiated phenotypes in vivo and in vitro. An Oct4 activation domain fusion supported embryonic stem cell self-renewal in vitro at lower concentrations than that required for Oct4 while alleviating the ordinary requirement for the cytokine LIF. At still lower levels of the fusion, LIF dependence was restored. We conclude that the necessary and sufficient function of Oct4 in promoting pluripotency is to activate specific target genes. 相似文献
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Rapid induction of pluripotency genes after exposure of human somatic cells to mouse ES cell extracts 总被引:5,自引:0,他引:5
Bru T Clarke C McGrew MJ Sang HM Wilmut I Blow JJ 《Experimental cell research》2008,314(14):2634-2642
The expression of 4 pluripotency genes (Oct4, Sox2, c-Myc and Klf4) in mouse embryonic fibroblasts can reprogramme them to a pluripotent state. We have investigated the expression of these pluripotency genes when human somatic 293T cells are permeabilized and incubated in extracts of mouse embryonic stem (ES) cells. Expression of all 4 genes was induced over 1–8 h. Gene expression was associated with loss of repressive histone H3 modifications and increased recruitment of RNA polymerase II at the promoters. Lamin A/C, which is typically found only in differentiated cells, was also removed from the nuclei. When 293T cells were returned to culture after exposure to ES cell extract, the expression of the pluripotency genes continued to rise over the following 48 h of culture, suggesting that long-term reprogramming of gene expression had been induced. This provides a methodology for studying the de-differentiation of somatic cells that can potentially lead to an efficient way of reprogramming somatic cells to a pluripotent state without genetically altering them. 相似文献