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

基本信息

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
项目类别：
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

项目摘要

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，内耳毛细胞的丧失会导致听力和平衡障碍，因为这些细胞会影响听力和平衡能力。不再生。相比之下，在非哺乳动物脊椎动物中，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 Corwin首先在两栖动物侧系中通过直接证明细胞通过转分化使用延时成像进行观察，但更间接的方法也发现鸟类身上也发生了类似的过程基底乳头。这些结果共同表明，内耳的毛细胞再生问题哺乳动物可以概括为两个基本问题：（1）是什么导致了支持增殖的丧失 (2) 是什么限制了支持细胞向新毛细胞的转分化？在这个拨款申请我们的目的是研究限制前庭系统再生的因素有哪些哺乳动物。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。我们将专门针对嵴（位于大脑底部的感觉区域）进行研究。三个半规管），用于检测三个顺序平面中的头部旋转。随着人口老龄化的平衡疾病变得更加普遍，这个器官对于维持凝视尤为重要。嵴迄今为止，我们已经在分子水平上进行了深入研究，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产生毛细胞。