Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305.
Department of Special Education and Communication Disorders, College of Education and Human Sciences, University of Nebraska, Lincoln, NE 68583.
Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2116973119. doi: 10.1073/pnas.2116973119. Epub 2022 Apr 5.
Sensory hair cells (HCs) in the utricle are mechanoreceptors required to detect linear acceleration. After damage, the mammalian utricle partially restores the HC population and organ function, although regenerated HCs are primarily type II and immature. Whether native, surviving HCs can repair and contribute to this recovery is unclear. Here, we generated the Pou4f3DTR/+; Atoh1CreERTM/+; Rosa26RtdTomato/+ mouse to fate map HCs prior to ablation. After HC ablation, vestibular evoked potentials were abolished in all animals, with ∼57% later recovering responses. Relative to nonrecovery mice, recovery animals harbored more Atoh1-tdTomato+ surviving HCs. In both groups, surviving HCs displayed markers of both type I and type II subtypes and afferent synapses, despite distorted lamination and morphology. Surviving type II HCs remained innervated in both groups, whereas surviving type I HCs first lacked and later regained calyces in the recovery, but not the nonrecovery, group. Finally, surviving HCs initially displayed immature and subsequently mature-appearing bundles in the recovery group. These results demonstrate that surviving HCs are capable of self-repair and may contribute to the recovery of vestibular function.
感觉毛细胞(HCs)在耳石器中是检测线性加速度所必需的机械感受器。在损伤后,哺乳动物的耳石器部分恢复了 HCs 群体和器官功能,尽管再生的 HCs 主要是 II 型和未成熟的。内源性、存活的 HCs 是否能够修复并有助于这种恢复尚不清楚。在这里,我们生成了 Pou4f3DTR/+; Atoh1CreERTM/+; Rosa26RtdTomato/+ 小鼠,以便在消融前对 HCs 进行命运图谱分析。在 HCs 消融后,所有动物的前庭诱发电位都被消除,其中约 57%的动物随后恢复了反应。与未恢复的动物相比,恢复的动物中存活的 Atoh1-tdTomato+ HCs 更多。在两组动物中,存活的 HCs 均显示出 I 型和 II 型亚型和传入神经突触的标志物,尽管分层和形态扭曲。在两组动物中,存活的 II 型 HCs 都保持着神经支配,而存活的 I 型 HCs 首先在恢复组中缺乏而后来又恢复了 calyces,但在非恢复组中没有。最后,存活的 HCs 在恢复组中最初显示出不成熟的束,后来则显示出成熟的束。这些结果表明,存活的 HCs 具有自我修复的能力,并可能有助于前庭功能的恢复。