Rps14 upregulation promotes inner ear progenitor proliferation and hair cell regeneration in the neonatal mouse cochlea.

Rps14 upregulation promotes inner ear progenitor proliferation and hair cell regeneration in the neonatal mouse cochlea.
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DOI:
10.1111/cpr.13458
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发表时间:
2023-05
期刊:
影响因子:
8.5
通讯作者:
--
中科院分区:
生物学1区
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--
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感觉神经性听力损失是由毛细胞损伤引起的,由于缺乏毛细胞再生,哺乳动物的毛细胞损伤是不可逆的,但最近的研究表明Lgr5 +支持细胞是能够再生毛细胞的祖细胞。RPS14(核糖体蛋白S14)是一种40S核糖体亚基成分,与红细胞分化有关,在本研究中,我们使用一种新型腺相关病毒内耳系统上调培养毛细胞祖细胞中RPS14的表达,并观察到其增殖和向毛细胞分化的能力增强。同样,Rps14在小鼠耳蜗中的过表达可以通过激活Wnt信号通路来促进支持细胞的增殖。此外,过表达Rps14诱导了Corti器官的毛细胞再生,谱系追踪显示新的毛细胞是从Lgr5+祖细胞转化而来的。总之,我们的分析揭示了Rps14在促进哺乳动物毛细胞再生中的潜在作用。在这项工作中,Xu等人使用腺相关病毒-内耳介导的基因过表达方法研究了Rps14上调对支持细胞增殖和分化能力的影响。在这项研究中,Xu等人利用类器官和耳蜗组织模拟支持细胞产生有丝分裂毛细胞和非有丝分裂毛细胞,发现Rps14的重新表达加速了支持细胞可塑性的发育上升,并使支持细胞能够产生新的毛细胞。
Sensorineural hearing loss a result from hair cell damage, which is irreversible in mammals owing to the lack of hair cell regeneration, but recent researches have shown that Lgr5 + supporting cells are progenitors capable of regenerating hair cells. RPS14 (ribosomal protein S14) is a 40S ribosomal subunit component and is associated with erythrocyte differentiation, and in this study, we used a novel adeno‐associated virus‐inner ear system to upregulate Rps14 expression in cultured hair cell progenitors and observed an enhancement on their ability to proliferate and differentiate into hair cells. Similarly, Rps14 overexpression in the mice cochlea could promote supporting cells proliferation by activating the Wnt signalling pathway. In addition, over‐expressing Rps14 induced hair cells regeneration in the organ of Corti, and lineage tracing showed that the new hair cells had transformed from Lgr5+ progenitors. In conclusion, our analysis reveals the potential role of Rps14 in driving hair cell regeneration in mammalian. In this work, Xu et al investigated the effect of Rps14 upregulation on the proliferation and differentiation abilities of supporting cells using an adeno‐associated virus‐inner ear‐mediated gene overexpression approach. In this study, using organoid and cochlear tissue to model mitotic and nonmitotic hair cell production by supporting cells, Xu et al found that re‐expression of Rps14 accelerated the developmental rise in supporting cell plasticity and rendered supporting cells capable of producing new hair cells.
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