Conversion of stem cells to cell types of the inner ear

描述（由申请人提供）：哺乳动物内耳的神经元和感觉细胞一旦受到毒素、过度噪音或感染因子的损伤就不能再生。最近发现小鼠胚胎干细胞（ES）可以在体外诱导分化为内耳感觉细胞，这为表征从干细胞发育为内耳细胞的途径提供了基础。将研究促进这种分化的基因，并将在干细胞祖细胞中选择性表达这些基因，以确定产生毛细胞和螺旋神经节神经元的最佳条件。将开发一种测定系统，其使用与由候选基因和内耳基因文库的表达诱导的细胞分化相关的报告构建体。然后，这些信息将用于从人类ES细胞中产生内耳细胞，所得细胞将成为移植的候选细胞。分化的信息也将是有用的，在未来尝试激活内源性干细胞无论是小分子或基因传递。长期目标是开发可以替代因变性而丢失的细胞的疗法。

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.