Stem Cell Differentiation in the Auditory System

听觉系统中的干细胞分化

• 批准号: 6851803
• 负责人: VALERIE D DEWULF
• 金额: $ 3.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6851803
• 关键词: auditory pathways; biomarker; cell differentiation; chick embryo; developmental neurobiology; ear hair cell; embryonic stem cell; genetic markers; genetically modified animals; hearing; immunocytochemistry; laboratory mouse; labyrinth; nerve stem cell; neuroanatomy; organ of Corti; otocyst /otolith; polymerase chain reaction; postdoctoral investigator; regeneration; stem cell transplantation; tissue /cell culture

DESCRIPTION (provided by applicant): Both Embryonic Stem (ES) cells and Neural Epithelial Progenitor (NEP) cells have been well characterized and generate a diversity of cell types in vivo and in vitro. Traditionally, the acquisition of cell fate by stem cells was thought to be a process of sequential restriction in the developmental potential. However, recent studies suggest that, under the appropriate circumstances, stem cells can be reprogrammed to acquire a broader developmental potential than had originally been specified. The two experiments described in this proposal seek to test the competence of a variety of stem cells to generate sensory hair cells. First, stem cells derived from transgenic mice will be cultured under specific conditions, developed in our laboratory, that promote progenitor proliferation and hair cell differentiation (Specific Aim 1). Second, stem cells will be grafted into a developing otocyst to test the capacity of stem cells to differentiate into hair cells when exposed to the full complement of factors that regulate hair cell differentiation in vivo (Specific Aim 2). These data will indicate whether all or only a sub-set of progenitors are capable of generating cells of the inner ear. In addition, these experiments are a first step in exploring the possibility of hair cell regeneration via stem cell transplantation and differentiation.

描述（由申请人提供）：胚胎干细胞（ES）和神经上皮祖细胞（NEP）细胞已经被很好地表征并在体内和体外产生多种细胞类型。传统上，干细胞获得细胞命运被认为是发育潜能的顺序限制过程。然而，最近的研究表明，在适当的情况下，干细胞可以被重新编程以获得比最初指定的更广泛的发育潜力。本提案中描述的两个实验旨在测试各种干细胞产生感觉毛细胞的能力。首先，来自转基因小鼠的干细胞将在我们实验室开发的特定条件下培养，促进祖细胞增殖和毛细胞分化（specific Aim 1）。其次，将干细胞移植到发育中的耳囊肿中，以测试当暴露于体内调节毛细胞分化的充分补充因子时，干细胞向毛细胞分化的能力（Specific Aim 2）。这些数据将表明是所有祖细胞还是只有一小部分祖细胞能够产生内耳细胞。此外，这些实验是探索通过干细胞移植和分化实现毛细胞再生可能性的第一步。