Li Qiang, Lex Rachel K, Chung HaeWon, Giovanetti Simone M, Ji Zhicheng, Ji Hongkai, Person Maria D, Kim Jonghwan, Vokes Steven A
From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
J Biol Chem. 2016 Mar 25;291(13):7171-82. doi: 10.1074/jbc.M116.714857. Epub 2016 Jan 21.
The Hedgehog (HH) signaling pathway is essential for the maintenance and response of several types of stem cells. To study the transcriptional response of stem cells to HH signaling, we searched for proteins binding to GLI proteins, the transcriptional effectors of the HH pathway in mouse embryonic stem (ES) cells. We found that both GLI3 and GLI1 bind to the pluripotency factor NANOG. The ectopic expression of NANOG inhibits GLI1-mediated transcriptional responses in a dose-dependent fashion. In differentiating ES cells, the presence of NANOG reduces the transcriptional response of cells to HH. Finally, we found thatGli1andNanogare co-expressed in ES cells at high levels. We propose that NANOG acts as a negative feedback component that provides stem cell-specific regulation of the HH pathway.
刺猬索尼克（HH）信号通路对于多种类型干细胞的维持和反应至关重要。为了研究干细胞对HH信号的转录反应，我们在小鼠胚胎干细胞（ES细胞）中寻找与HH信号通路的转录效应因子GLI蛋白结合的蛋白质。我们发现GLI3和GLI1都与多能性因子NANOG结合。NANOG的异位表达以剂量依赖的方式抑制GLI1介导的转录反应。在分化的ES细胞中，NANOG的存在降低了细胞对HH的转录反应。最后，我们发现Gli1和Nanog在ES细胞中高水平共表达。我们提出，NANOG作为一种负反馈成分，对HH信号通路进行干细胞特异性调节。
