Alteration of Musashi1 Intra-cellular Distribution During Regeneration Following Gentamicin-Induced Hair Cell Loss in the Guinea Pig Crista Ampullaris
Alteration of Musashi1 Intra-cellular Distribution During Regeneration Following Gentamicin-Induced Hair Cell Loss in the Guinea Pig Crista Ampullaris
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DOI：
10.3389/fncel.2019.00481
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发表时间：
2019-10-25
影响因子：
5.3
通讯作者：
Yamasoba, Tatsuya
中科院分区：
文献类型：
--
作者：
Kinoshita, Makoto;Fujimoto, Chisato;Yamasoba, Tatsuya
哺乳动物内耳毛细胞（HC）再生的机制仍有争议。了解哪些分子调节成熟哺乳动物的HC再生将是治疗内耳疾病的关键。Musashi 1（MSI 1）是一种RNA结合蛋白，作为Notch-1信号通路的调节剂，与不对称分裂和维持干细胞功能相关。在这项研究中，我们研究了细胞增殖活性和MSI 1表达的时空模式的变化在庆大霉素（GM）处理的豚鼠壶腹嵴（CA）。虽然前庭毛细胞在CA几乎消失后14天，在内耳注射GM，前庭毛细胞的密度自发增加了高达50%，相对于对照组在56天后GM治疗（PT）。与PT 14天相比，PT 28天时II型HC的数量显著增加（p < 0.01），而I型HC或支持细胞（SC）的数量没有变化。在整个观察期内，SC的数量没有变化。溴脱氧尿苷与相同的GM处理的管理表明，在PT的14和28天之间的SC中的细胞增殖活性高。GM处理后HC自发再生过程中MSI 1表达的时空模式变化显示，在PT 7-21天，MSI 1免疫反应性扩散到SC的细胞质中，而在其他时间段，MSI 1的表达仅限于SC的细胞核。在PT 21天时观察到MSI 1/MYO 7A双阳性细胞。这些结果表明，前庭HC的再生可能起源于SC的不对称细胞分裂和分化，MSI 1可能参与控制前庭HC的再生过程。
The mechanism underlying hair cell (HC) regeneration in the mammalian inner ear is still under debate. Understanding what molecules regulate the HC regeneration in mature mammals will be the key to the treatment of the inner ear disorder. Musashi1 (MSI1) is an RNA binding protein associated with asymmetric division and maintenance of stem cell function as a modulator of the Notch-1 signaling pathway. In this study, we investigated the cellular proliferative activity and changes in spatiotemporal pattern of MSI1 expression in the gentamicin (GM)-treated crista ampullaris (CA) in guinea pigs. Although the vestibular HCs in the CA almost disappeared at 14 days after injecting GM in the inner ear, the density of vestibular HCs spontaneously increased by up to 50% relative to controls at 56 days post-GM treatment (PT). The number of the type II HCs was significantly increased at 28 days PT relative to 14 days PT (p < 0.01) while that of type I HCs or supporting cells (SCs) did not change. The number of SCs did not change through the observational period. Administration of bromodeoxyuridine with the same GM treatment showed that the cell proliferation activity was high in SCs between 14 and 28 days PT. The changes in spatiotemporal patterns of MSI1 expression during spontaneous HC regeneration following GM treatment showed that MSI1-immunoreactivity was diffusely spread into the cytoplasm of the SCs during 7-21 days PT whereas the expression of MSI1 was confined to the nucleus of SCs in the other period. The MSI1/MYO7A double-positive cells were observed at 21 days PT. These results suggest that regeneration of vestibular HCs might originate in the asymmetric cell division and differentiation of SCs and that MSI1 might be involved in controlling the process of vestibular HC regeneration.