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The accessible chromatin landscape of the human genome 总被引:2,自引:0,他引:2
RE Thurman E Rynes R Humbert J Vierstra MT Maurano E Haugen NC Sheffield AB Stergachis H Wang B Vernot K Garg S John R Sandstrom D Bates L Boatman TK Canfield M Diegel D Dunn AK Ebersol T Frum E Giste AK Johnson EM Johnson T Kutyavin B Lajoie BK Lee K Lee D London D Lotakis S Neph F Neri ED Nguyen H Qu AP Reynolds V Roach A Safi ME Sanchez A Sanyal A Shafer JM Simon L Song S Vong M Weaver Y Yan Z Zhang Z Zhang B Lenhard M Tewari MO Dorschner RS Hansen PA Navas G Stamatoyannopoulos VR Iyer 《Nature》2012,489(7414):75-82
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Bendall SC Stewart MH Menendez P George D Vijayaragavan K Werbowetski-Ogilvie T Ramos-Mejia V Rouleau A Yang J Bossé M Lajoie G Bhatia M 《Nature》2007,448(7157):1015-1021
Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment. Here, we demonstrate that self-renewal and pluripotent properties of human embryonic stem (ES) cells depend on a dynamic interplay between human ES cells and autologously derived human ES cell fibroblast-like cells (hdFs). Human ES cells and hdFs are uniquely defined by insulin-like growth factor (IGF)- and fibroblast growth factor (FGF)-dependence. IGF 1 receptor (IGF1R) expression was exclusive to the human ES cells, whereas FGF receptor 1 (FGFR1) expression was restricted to surrounding hdFs. Blocking the IGF-II/IGF1R pathway reduced survival and clonogenicity of human ES cells, whereas inhibition of the FGF pathway indirectly caused differentiation. IGF-II is expressed by hdFs in response to FGF, and alone was sufficient in maintaining human ES cell cultures. Our study demonstrates a direct role of the IGF-II/IGF1R axis on human ES cell physiology and establishes that hdFs produced by human ES cells themselves define the stem cell niche of pluripotent human stem cells. 相似文献
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