OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition
OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition
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DOI：
10.1016/j.celrep.2016.04.020
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发表时间：
2016-05-10
期刊：
影响因子：
8.8
通讯作者：
Masui, Shinji
中科院分区：
文献类型：
--
作者：
Kitazawa, Koji;Hikichi, Takafusa;Masui, Shinji
在发育过程中，胚胎外胚层分化为神经外胚层和表面外胚层的机制尚不清楚。在这里，我们表明转录因子OVOL2维持人类角膜上皮细胞（cec）的转录程序，cec是表面外胚层的衍生物，并且OVOL2可能调节两种谱系的差异转录程序。功能性筛选鉴定OVOL2是维持CECs的间充质基因的抑制因子。OVOL2与其他转录因子的转导可诱导成纤维细胞中CECs的转录程序。此外，发现神经外胚层衍生物表达间充质基因，单独OVOL2可以通过抑制这些基因而激活上皮基因来诱导神经祖细胞中CECs的转录程序。我们的数据表明，一些神经外胚层和表面外胚层衍生细胞的转录程序之间的差异可能部分受到上皮和间充质基因之间相互抑制机制的调节，正如在上皮到间充质转化中所看到的那样。
In development, embryonic ectoderm differentiates into neuroectoderm and surface ectoderm using poorly understood mechanisms. Here, we show that the transcription factor OVOL2 maintains the transcriptional program of human corneal epithelium cells (CECs), a derivative of the surface ectoderm, and that OVOL2 may regulate the differential transcriptional programs of the two lineages. A functional screen identified OVOL2 as a repressor of mesenchymal genes to maintain CECs. Transduction of OVOL2 with several other transcription factors induced the transcriptional program of CECs in fibroblasts. Moreover, neuroectoderm derivatives were found to express mesenchymal genes, and OVOL2 alone could induce the transcriptional program of CECs in neural progenitors by repressing these genes while activating epithelial genes. Our data suggest that the difference between the transcriptional programs of some neuroectoderm-and surface ectoderm-derivative cells may be regulated in part by a reciprocally repressive mechanism between epithelial and mesenchymal genes, as seen in epithelial-to-mesenchymal transition.