Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells
Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells
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产后哺乳动物前庭毛细胞发育和再生的不协调成熟
DOI：
10.1371/journal.pbio.3000326
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发表时间：
2019-07
期刊：
影响因子：
9.8
通讯作者：
Alan G Cheng
中科院分区：
文献类型：
--
作者：
Tian Wang;Mamiko Niwa;Zahra N Sayyid;Davood K Hosseini;Nicole Pham;Sherri M Jones;Anthony J Ricci;Alan G Cheng
感觉毛细胞是听觉和平衡功能所需的机械感受器。从胚胎发育开始，毛细胞获得用于机械感觉的顶端静纤毛束、形成受体电位的基底外侧离子通道和用于集中传递信息的突触接触。这些关键的成熟步骤是连续的，并假定耦合;然而，毛细胞出生后是否出现类似的成熟是未知的。在这里，我们表明，在体内出生后产生和再生的毛细胞在椭圆囊，前庭器官检测线性加速度，获得了一些成熟的躯体功能，但毛束出现无功能和短。椭圆囊由两种毛细胞亚型组成，具有不同的形态、电生理和突触特征。在未受损和受损的椭圆囊，命运映射和电生理学实验表明，Plp 1+支持细胞的基础上的分子标记，基底侧电导和突触特性II型毛细胞的属性，但立体纤毛束是不存在的，或小，无功能。相比之下，Lgr 5+支持细胞再生的毛细胞具有I型和II型特性，代表了不同的毛细胞前体亚型。最后，直接的生理测量表明，椭圆囊的功能取消的损害是部分恢复再生过程中。总之，我们的数据揭示了一个以前未被认识到的毛细胞的异常成熟程序生成和再生出生后，可能有广泛的影响内耳再生疗法。
Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.
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DOI：
10.1007/978-3-319-77525-8_100075
发表时间：
2018-12
期刊：
Encyclopedia of Big Data Technologies
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
通讯作者：
--
DOI：
10.1210/jcem.85.1.6229
发表时间：
2000
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1109/icmas.2000.858517
发表时间：
2000-07
期刊：
Proceedings Fourth International Conference on MultiAgent Systems
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Jones OD;Schall JD;Shen FX
通讯作者：
Shen FX