共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
3.
Sonia Stefanovic Nesrine Abboud Stéphanie Désilets David Nury Chad Cowan Michel Pucéat 《The Journal of cell biology》2009,186(5):665-673
Oct4 exerts a dose-dependent dual action, as both a gatekeeper for stem cell pluripotency and in driving cells toward specific lineages. Here, we identify the molecular mechanism underlying this dual function. BMP2- or transgene-induced Oct4 up-regulation drives human embryonic and induced pluripotent stem cells to become cardiac progenitors. When embryonic stem cell pluripotency is achieved, Oct4 switches from the Sox2 to the Sox17 promoter. This switch allows the cells to turn off the pluripotency Oct4-Sox2 loop and to turn on the Sox17 promoter. This powerful process generates a subset of endoderm-expressing Sox17 and Hex, both regulators of paracrine signals for cardiogenesis (i.e., Wnt, BMP2) released into the medium surrounding colonies of embryonic stem cells. Our data thus reveal a novel molecular Oct4- and Sox17-mediated mechanism that disrupts the stem cell microenvironment favoring pluripotency to provide a novel paracrine endodermal environment in which cell lineage is determined and commits the cells to a cardiogenic fate. 相似文献
4.
5.
6.
7.
8.
9.
10.
11.
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
12.
13.
14.
15.
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
16.
17.
18.
19.
Transcriptional regulation of nanog by OCT4 and SOX2 总被引:39,自引:0,他引:39
Rodda DJ Chew JL Lim LH Loh YH Wang B Ng HH Robson P 《The Journal of biological chemistry》2005,280(26):24731-24737