Competence of support cells to form hair cells in the mammalian inner ear

支持细胞在哺乳动物内耳中形成毛细胞的能力

• 批准号: 9914231
• 负责人: Olivia Mary Bermingham-McDonogh
• 金额: $ 43.64万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9914231
• 关键词: Adult; Affect; Age; Amphibia; Applications Grants; Auditory; Basilar Papilla; Birds; Cells; Chromatin; Cochlea; Competence; Corwin; Crista ampullaris; Data; Development; Epigenetic Process; Epithelial; Epithelium; Fishes; Gene Expression; Gene Expression Profile; Genes; Grant; Hair Cells; Head; Human; Image; Labyrinth; Lead; Mammalian Cell; Mammals; Methods; Mitotic; Molecular; Mus; Natural regeneration; Newborn Infant; Organ; Organ of Corti; Outer Hair Cells; Pathway interactions; Play; Population; Process; Regenerative response; Reporter; Reporting; Resolution; Role; Rotation; Semicircular canal structure; Sensory; Sensory Hair; Signal Pathway; Signal Transduction; Supporting Cell; System; Techniques; Testing; Time; Time Study; Transgenic Mice; Transgenic Organisms; Vertebrates; base; equilibration disorder; experimental study; gaze; hair cell regeneration; hearing impairment; inhibitor/antagonist; lateral line; notch protein; overexpression; postnatal; regenerative; single-cell RNA sequencing; time use; transdifferentiation

Summary/Abstract In humans, loss of the hair cells in the inner ear leads to hearing and balance impairment, since these cells do not regenerate. By contrast, in non-mammalian vertebrates, like birds and fish, damaged auditory hair cells are regenerated very efficiently from the surrounding supporting cells. The ability of support cells to give rise to hair cells through transdifferentiation was first demonstrated by Corwin in the amphibian lateral line, by direct observation using time-lapse imaging, but more indirect methods also found a similar process to occur in bird basilar papilla. These results together suggest that the problem of hair cell regeneration in the inner ear of the mammal can be summarized in two fundamental questions: (1) What causes the loss in proliferation of support cells following damage and (2) what limits the transdifferentiation of the support cells to new hair cells? In this grant application we aim to study what are the factors that limit regeneration in the vestibular system of the mammal. We will use various transgenic strains to activate pathways that may lead to stimulation of hair cell regeneration. We will specifically direct our studies towards the crista (the sensory regions at the base of the three semicircular canals) that detect head rotation in the three ordinal planes. As the population ages balance disorders become more prevalent and this organ is particularly important for maintaining gaze. The cristae have been understudied at the molecular level to date and we have recently developed a culture method and are using advanced molecular techniques to elucidate changes in the competence of crista support cells to generate hair cells.

摘要/摘要 在人类中，内耳毛细胞的损失会导致听力和平衡障碍，因为这些细胞 而不是再生。相比之下，在非哺乳类脊椎动物中，如鸟类和鱼类，受损的听觉毛细胞 从周围的支持细胞中非常有效地再生。支持细胞产生毛发的能力 细胞通过转分化首先由Corwin在两栖动物侧线中证明，通过直接 使用延时成像进行观察，但更间接的方法也发现了类似的过程发生在鸟类身上 基底乳头这些结果共同表明，内耳毛细胞再生的问题， 哺乳动物可以概括为两个基本问题：（1）是什么原因导致支持扩散的损失 （2）是什么限制了支持细胞向新毛细胞的转分化？在这 我们的目标是研究限制前庭系统再生的因素是什么。 哺乳动物。我们将使用各种转基因菌株来激活可能导致毛细胞刺激的途径 再生我们将专门针对我们的研究对嵴（在基地的感觉区， 三个半规管），其检测头部在三个有序平面中的旋转。随着人口老龄化的平衡 疾病变得更加普遍，并且该器官对于保持凝视特别重要。嵴 到目前为止，在分子水平上的研究还不够，我们最近开发了一种培养方法， 正在使用先进的分子技术来阐明嵴支持细胞能力的变化， 生成毛细胞。