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PLoS Genet. 2018 Jul 31;14(7):e1007552. doi: 10.1371/journal.pgen.1007552. eCollection 2018 Jul.
2
The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex.组蛋白去甲基化酶LSD1通过与Pax2和NuRD阻遏复合物相互作用来调节内耳祖细胞的分化。
PLoS One. 2018 Jan 25;13(1):e0191689. doi: 10.1371/journal.pone.0191689. eCollection 2018.
3
Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea.刺猬信号通路促进新生小鼠耳蜗中祖细胞的增殖及随后的毛细胞形成。
Front Mol Neurosci. 2017 Dec 21;10:426. doi: 10.3389/fnmol.2017.00426. eCollection 2017.
4
Otoferlin acts as a Ca sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses.耳毛细胞带状突触中,otoferlin 作为囊泡融合和囊泡池补充的 Ca 传感器发挥作用。
Elife. 2017 Nov 7;6:e31013. doi: 10.7554/eLife.31013.
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Claudin expression in the rat endolymphatic duct and sac - first insights into regulation of the paracellular barrier by vasopressin.水通道蛋白在大鼠内淋巴管和囊中的表达——血管加压素对细胞旁屏障调节的初步认识。
Sci Rep. 2017 Apr 4;7:45482. doi: 10.1038/srep45482.
6
Atoh1 as a Coordinator of Sensory Hair Cell Development and Regeneration in the Cochlea.Atoh1作为耳蜗中感觉毛细胞发育和再生的协调因子。
Chonnam Med J. 2017 Jan;53(1):37-46. doi: 10.4068/cmj.2017.53.1.37. Epub 2017 Jan 25.
7
Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs.耳蜗和前庭器官的祖细胞向内耳细胞类型分化的独特能力。
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8
Extensive Supporting Cell Proliferation and Mitotic Hair Cell Generation by In Vivo Genetic Reprogramming in the Neonatal Mouse Cochlea.新生小鼠耳蜗体内基因重编程诱导支持细胞广泛增殖和有丝分裂毛细胞生成
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Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea.Wnt和Notch信号通路在调控耳蜗毛细胞再生中的作用。
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Co-regulation of the Notch and Wnt signaling pathways promotes supporting cell proliferation and hair cell regeneration in mouse utricles.Notch 和 Wnt 信号通路的共调控促进小鼠耳石中支持细胞的增殖和毛细胞的再生。
Sci Rep. 2016 Jul 20;6:29418. doi: 10.1038/srep29418.

小鼠耳蜗中诱导毛细胞转录组的特征分析。

Characterization of the transcriptomes of -induced hair cells in the mouse cochlea.

作者信息

Liu Li-Man, Zhao Li-Ping, Wu Ling-Jie, Guo Luo, Li Wen-Yan, Chen Yan

机构信息

ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, Fudan University Shanghai 200031, China.

NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai 200031, China.

出版信息

Am J Stem Cells. 2020 Feb 15;9(1):1-15. eCollection 2020.

PMID:32211215
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7076321/
Abstract

Postnatal mammalian cochlear hair cells (HCs) can be regenerated by direct transdifferentiation or by mitotic regeneration from supporting cells through many pathways, including Atoh1, Wnt, Hedgehog and Notch signaling. However, most new HCs are immature HCs. In this study we used RNA-Seq analysis to compare the differences between the transcriptomes of overexpression-induced new HCs and the native HCs, and to define the factors that might help to promote the maturation of new HCs. As expected, we found -induced new HCs had obvious HC characteristics as demonstrated by the expression of HC markers such as and Myosin VIIA (Myo7a). However, -induced new HCs had significantly lower expression of genes that are related to HC function such as Slc26a5 (), and . We found that genes related to HC cell differentiation and maturation (, , , , , , , , etc.) had significantly lower expression levels in new HCs compared to native HCs. In conclusion, we found a set of genes that might regulate the differentiation and maturation of new HCs, and these genes might serve as potential new therapeutic targets for functional HC regeneration and hearing recovery.

摘要

出生后的哺乳动物耳蜗毛细胞(HCs)可通过直接转分化或通过支持细胞经有丝分裂再生,再生途径包括Atoh1、Wnt、Hedgehog和Notch信号通路等多种。然而,大多数新生HCs是未成熟的HCs。在本研究中,我们使用RNA测序分析来比较过表达诱导产生的新生HCs与天然HCs转录组之间的差异,并确定可能有助于促进新生HCs成熟的因素。正如预期的那样,我们发现过表达诱导产生的新生HCs具有明显的HC特征,如通过HC标记物如和肌球蛋白VIIA(Myo7a)的表达所证明。然而,过表达诱导产生的新生HCs中与HC功能相关的基因如Slc26a5()、和的表达显著较低。我们发现,与HC细胞分化和成熟相关的基因(、、、、、、、、等)在新生HCs中的表达水平与天然HCs相比显著较低。总之,我们发现了一组可能调节新生HCs分化和成熟的基因,这些基因可能成为功能性HC再生和听力恢复的潜在新治疗靶点。