Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea.
Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea.
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Hedgehog 信号促进新生小鼠耳蜗祖细胞的增殖和随后毛细胞的形成
DOI：
10.3389/fnmol.2017.00426
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发表时间：
2017
影响因子：
4.8
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Chen Y;Lu X;Guo L;Ni W;Zhang Y;Zhao L;Wu L;Sun S;Zhang S;Tang M;Li W;Chai R;Li H
毛细胞（HC）的损失是哺乳动物永久性感音神经性听力损失的主要原因。与低等脊椎动物不同，哺乳动物耳蜗毛细胞在损伤后不能自发再生，尽管前庭系统确实保持有限的毛细胞再生能力。因此，从受损的感觉上皮再生HC一直是听力恢复领域的主要研究领域之一。Hedgehog信号在内耳胚胎发育过程中起着重要作用，参与了前体细胞的增殖、分化以及细胞命运的决定。在这项研究中，我们表明，重组的Sonic Hedgehog（Shh）蛋白有效地促进球的形成，增殖和分化的LGR 5+祖细胞分离的新生小鼠耳蜗。为了进一步探索这一点，我们确定了Hedgehog信号传导对来自转基因R26-SmoM 2小鼠的培养耳蜗外植体中的细胞增殖和HC再生的影响，所述转基因R26-SmoM 2小鼠组成性地激活耳蜗支持细胞中的Hedgehog信号传导。在没有新霉素处理的情况下，Hedgehog信号传导的上调没有显著促进细胞增殖或新HC形成。然而，损伤后的感觉上皮细胞的新霉素治疗，过度激活的刺猬信号导致显着的支持细胞增殖和HC再生的耳蜗上皮外植体。通过RNA测序和实时荧光定量PCR比较对照小鼠和R26-SmoM 2小鼠耳蜗的转录本，鉴定出参与增殖和分化过程的多个基因。这项研究对于通过操纵Hedgehog信号通路治疗感音神经性听力损失具有重要意义。
Hair cell (HC) loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh) protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway.
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影响因子：
3.7
作者：
Jahan I;Pan N;Kersigo J;Fritzsch B
通讯作者：
Fritzsch B
影响因子：
5.3
作者：
Cogliati, T;Good, DJ;Kirsch, IR
通讯作者：
Kirsch, IR
DOI：
10.1073/pnas.1222341110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Bok, Jinwoong;Zenczak, Colleen;Wu, Doris K.
通讯作者：
Wu, Doris K.
影响因子：
4
作者：
Chen, Jianguo;Shen, Chaoyan;Huang, Qingfeng
通讯作者：
Huang, Qingfeng
DOI：
10.1523/jneurosci.0312-08.2008
发表时间：
2008-07-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Driver EC;Pryor SP;Hill P;Turner J;Rüther U;Biesecker LG;Griffith AJ;Kelley MW
通讯作者：
Kelley MW