Conversion of stem cells to cell types of the inner ear

描述(申请人提供)：哺乳动物内耳的神经元和感觉细胞一旦受到毒素、过度噪音或感染性因素的破坏就不能再生。最近发现小鼠胚胎干细胞在体外可以被诱导分化为内耳感觉细胞，这为描述干细胞向内耳细胞发育的途径提供了基础。将研究促进这种分化的基因，并将这些基因选择性地在干细胞前体细胞中表达，以确定产生毛细胞和螺旋神经节神经元的最佳条件。将开发一种检测系统，使用与候选基因和内耳基因库的表达诱导的细胞分化相关的报告构建物。然后，这些信息将被用来从人类ES细胞中产生内耳细胞，所产生的细胞将成为移植的候选细胞。有关分化的信息也将在未来用小分子或通过基因传递激活内源干细胞的尝试中有用。长期目标是开发能够替代因退化而丢失的细胞的治疗方法。

DESCRIPTION (provided by applicant): The neurons and sensory cells of the mammalian inner ear do not regenerate once they are damaged by toxins, excessive noise, or infectious agents. The recent discovery that mouse embryonic stem (ES) cells can be induced to differentiate into sensory cells of the inner ear in vitro provides a basis for characterizing the pathways by which this development from stem cell to inner ear cell occurs. The genes that promote this differentiation will be investigated and the genes will be selectively expressed in stem cell progenitors to determine the optimal conditions for generation of hair cells and spiral ganglion neurons. An assay system will be developed that uses reporter constructs that correlate to the cellular differentiation induced by the expression of both candidate genes and a library of inner ear genes. The information will then be used to produce inner ear cells from human ES cells and the resulting cells will be candidates for transplantation. The information on differentiation will also be useful in future attempts to activate endogenous stem cells either with small molecules or by gene delivery. The long term objective is to develop therapies that can replace cells lost to degeneration.