Repair of surviving hair cells in the damaged mouse utricle.
Repair of surviving hair cells in the damaged mouse utricle.
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DOI：
10.1073/pnas.2116973119
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发表时间：
2022-04-12
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管功能部分恢复，但哺乳动物椭圆囊的毛细胞再生有限。哺乳动物椭圆囊毛细胞损伤后，前庭诱发电位（椭圆囊功能的测量指标）恢复。虽然之前的研究表明，针对损伤的再生能力有限，但大多数再生毛细胞都是 II 型，具有未成熟的毛细胞束。剩余的毛细胞（“存活的毛细胞”）是否能够自我修复并有助于功能恢复尚不清楚。通过谱系追踪，我们对存活的毛细胞随时间的变化进行了表征，发现它们能够修复毛束、重新获得神经支配并保持分化，因此有望有助于器官功能的恢复。椭圆囊中的感觉毛细胞（HC）是检测线性加速度所需的机械感受器。受损后，哺乳动物椭圆囊部分恢复了 HC 群体和器官功能，尽管再生的 HC 主要是 II 型且不成熟。原生的、幸存的 HC 是否能够修复并促进这种恢复尚不清楚。在这里，我们生成了Pou4f3DTR/+； Atoh1CreERTM/+； Rosa26RtdTomato/+ 小鼠在消融前绘制命运图 HC。 HC 消融后，所有动物的前庭诱发电位均被消除，约 57% 随后恢复了反应。相对于未恢复的小鼠，恢复的动物拥有更多的 Atoh1-tdTomato+ 存活 HC。在两组中，尽管层压和形态扭曲，但幸存的 HC 都显示出 I 型和 II 型亚型以及传入突触的标记。两组中幸存的 II 型 HC 均保持受神经支配，而恢复组中幸存的 I 型 HC 首先缺乏肾盏，后来又重新获得肾盏，但非恢复组则不然。最后，幸存的 HC 最初表现出不成熟，随后在恢复组中表现出成熟的束。这些结果表明，存活的 HC 能够自我修复，并可能有助于前庭功能的恢复。
The mammalian utricle shows limited hair cell regeneration despite partial recovery of function. Recovery of vestibular evoked potentials, a measure of utricular function, occurs after utricular hair cell damage in mammals. While previous work has shown limited regeneration in response to damage, most regenerating hair cells are type II with immature-appearing bundles. Whether hair cells that remain (“surviving hair cells”) can self-repair and contribute to functional recovery is unknown. Using lineage tracing, we have characterized surviving hair cells over time and found that they repair bundles, regain innervation, and remain differentiated, and are therefore poised to contribute to the recovery of organ function. 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.
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影响因子：
2.8
作者：
Kawamoto K;Izumikawa M;Beyer LA;Atkin GM;Raphael Y
通讯作者：
Raphael Y
DOI：
10.1523/jneurosci.6274-11.2012
发表时间：
2012-05-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Burns JC;Cox BC;Thiede BR;Zuo J;Corwin JT
通讯作者：
Corwin JT
DOI：
10.1007/s101620020018
发表时间：
2002-06-01
影响因子：
2.4
作者：
Boyle, R;Highstein, SM;Xu, JP
通讯作者：
Xu, JP
影响因子：
2.1
作者：
Kariya, Shin;Hizli, Omer;Cureoglu, Sebahattin
通讯作者：
Cureoglu, Sebahattin
DOI：
10.1002/neu.10002
发表时间：
2002-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Gale, JE;Meyers, JR;Corwin, JT
通讯作者：
Corwin, JT