In Vitro Differentiation of Inner Ear Hair Cells

描述（由申请人提供）：成人感觉神经性耳聋是 主要是由于内耳中感觉毛细胞的永久性丧失。在 在这方面，哺乳动物不同于低等脊椎动物，后者可以再生感觉器官。 毛细胞从邻近的支持细胞中分离出来。目前还不知道是否 这种差异源于缺乏感觉发育能力， 哺乳动物支持细胞，或缺乏一些内源性刺激，在哺乳动物 来刺激耳部损伤后的再生本文中描述的实验 一项提案将标记胚胎感觉和支持细胞前体， 荧光转基因这些前体将从胚胎中纯化， 荧光激活细胞分选（FACS）和体外分化，使用 近年来发展的文化体系。该系统还将用于隔离和 从胚胎和出生后分化有丝分裂后支持细胞 动物从这些实验中，将确定是否有丝分裂后 哺乳动物的支持细胞能够产生感觉毛细胞，如果是这样，如何 这种能力在发展过程中长期存在。

DESCRIPTION (provided by applicant): Sensorineural deafness in adults is primarily due to the permanent loss of sensory hair cells in the inner ear. In this regard, mammals differ from lower vertebrates, which can regenerate sensory hair cells from adjacent supporting cells after injury. It is not known whether this difference arises from a lack of sensory developmental capacity in mammalian support cells, or from a lack of some endogenous stimulus in mammals to provoke regeneration after otic injury. Experiments described in this proposal will mark embryonic sensory and support cell precursors with a fluorescent transgene. These precursors will be purified from embryos using fluorescence activated cell sorting (FACS) and differentiated in vitro, using a recently developed culture system. This system will also be used to isolate and differentiate post-mitotic support cells from embryos and from post-natal animals. From these experiments, it will be determined whether post-mitotic mammalian support cells are able to generate sensory hair cells, and if so, how long in development this capacity persists.