Inner Ear Hair Cell-Like Cells from Human Embryonic Stem Cells
Inner Ear Hair Cell-Like Cells from Human Embryonic Stem Cells
复制标题
DOI：
10.1089/scd.2014.0033
复制
发表时间：
2014-06-01
影响因子：
4
通讯作者：
Heller, Stefan
中科院分区：
文献类型：
--
作者：
Ronaghi, Mohammad;Nasr, Marjan;Heller, Stefan
在哺乳动物中，多种形式的永久性听力损失是由于内耳无法替代丢失的感觉毛细胞造成的。在这里，我们应用分化策略，利用化学定义的附着基质条件，引导人类胚胎干细胞 (hESC) 分化为耳系细胞。人耳祖细胞的产生依赖于成纤维细胞生长因子（FGF）信号传导，长期培养会导致指示分化的内耳感觉上皮的标记物上调。使用基于鼠 Atoh1 增强子的转基因 ESC 报告系，我们发现分化的毛细胞样细胞同时表达多个毛细胞标记。毛细胞样细胞表现出让人想起立体纤毛束的突起，但未能完全成熟为具有典型毛细胞细胞结构的细胞。我们得出的结论是，可以在体外使用优化的限定条件来获得耳祖细胞规范和感觉细胞分化。
In mammals, the permanence of many forms of hearing loss is the result of the inner ear's inability to replace lost sensory hair cells. Here, we apply a differentiation strategy to guide human embryonic stem cells (hESCs) into cells of the otic lineage using chemically defined attached-substrate conditions. The generation of human otic progenitor cells was dependent on fibroblast growth factor (FGF) signaling, and protracted culture led to the upregulation of markers indicative of differentiated inner ear sensory epithelia. Using a transgenic ESC reporter line based on a murine Atoh1 enhancer, we show that differentiated hair cell-like cells express multiple hair cell markers simultaneously. Hair cell-like cells displayed protrusions reminiscent of stereociliary bundles, but failed to fully mature into cells with typical hair cell cytoarchitecture. We conclude that optimized defined conditions can be used in vitro to attain otic progenitor specification and sensory cell differentiation.