Retinoic acid and bone morphogenetic protein signaling synergize to efficiently direct epithelial differentiation of human embryonic stem cells
Retinoic acid and bone morphogenetic protein signaling synergize to efficiently direct epithelial differentiation of human embryonic stem cells
复制标题
DOI：
10.1634/stemcells.2007-0501
复制
发表时间：
2008-02-01
期刊：
影响因子：
5.2
通讯作者：
Palecek, Sean P.
中科院分区：
文献类型：
--
作者：
Metallo, Christian M.;Ji, Lin;Palecek, Sean P.
人胚胎干细胞（hESC）可以分化为各种体细胞谱系，包括复层鳞状上皮，尽管hESC上皮特化的分子机制目前仍不清楚。在这里，我们证明了一种新的，阶段特异性的影响，视黄酸（RA）上皮分化的人胚胎干细胞。RA强烈上调角蛋白18和转录因子p63的表达，这是参与表皮形态发生和外胚层规范，同时抑制早期神经标记转录。RA诱导的人胚胎干细胞有效地分化角蛋白14表达上皮细胞，虽然这种效果是依赖于骨形态发生蛋白信号的背景。此外，这些hESC衍生的角质形成细胞可以被传代培养以获得保留终末分化能力的相对纯的角质形成细胞群。这些发现表明RA在hESCs的上皮分化中起重要作用。
Human embryonic stem cells (hESCs) can differentiate to various somatic lineages, including stratified squamous epithelia, although the molecular mechanisms of epithelial specification from hESCs currently remain undefined. Here, we demonstrate a novel, stage-specific effect of retinoic acid (RA) on epithelial differentiation of hESCs. RA strongly upregulated expression of keratin 18 and the transcription factor p63, which is involved in epidermal morphogenesis and ectodermal specification, while repressing early neural marker transcription. RA-induced hESCs efficiently differentiated to keratin 14-expressing epithelial cells, although this effect was dependent upon on the context of bone morphogenetic protein signaling. Furthermore, these hESC-derived keratinocytes could be subcultured to obtain relatively pure keratinocyte populations that retained the capacity to terminally differentiate. These findings suggest that RA plays an important role in epithelial differentiation of hESCs.