The crosstalk between the Notch, Wnt, and SHH signaling pathways in regulating the proliferation and regeneration of sensory progenitor cells in the mouse cochlea.
The crosstalk between the Notch, Wnt, and SHH signaling pathways in regulating the proliferation and regeneration of sensory progenitor cells in the mouse cochlea.
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DOI：
10.1007/s00441-021-03493-w
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发表时间：
2021-11
影响因子：
3.6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Wu J;Li W;Guo L;Zhao L;Sun S;Li H
感觉毛细胞（HC）非常容易受到噪声、耳毒性药物和衰老的损害。虽然HC不能自发再生成年哺乳动物，以前的研究表明，信号通路参与HC再生受损的小鼠耳蜗。在这里，我们使用了Notch拮抗剂（DAPT），Wnt激动剂（QS 11），和重组Sonic hedgehog（SHH）蛋白，以研究它们在体内和体外新霉素诱导损伤后小鼠耳蜗HC再生的协同作用。使用DAPT，HC的数量增加，并且在完整和受损的耳蜗感觉上皮中均观察到支持细胞（SC）增殖，而这些数量在QS 11存在下没有变化。当同时用DAPT和QS 11处理时，HC的数量急剧增加，并且在耳蜗上皮中观察到更大的SC增殖。Notch 1条件性基因敲除和β-catenin过表达的转基因小鼠耳蜗SC增殖和HC再生明显高于Notch 1基因敲除和β-catenin过表达的转基因小鼠。当用DAPT、QS 11和SHH一起处理耳蜗时，SC增殖甚至更大，并且在HC区域和更大的上皮嵴中均观察到这种增殖。采用高通量RNA测序技术对各组间差异表达基因进行鉴定，结果显示SHH和Wnt信号通路参与了SC的增殖。我们的研究表明，Notch，Wnt和SHH信号通路的共同调节促进了小鼠耳蜗中广泛的细胞增殖和再生。在线版本包含补充材料，可通过10.1007/s 00441 -021-03493-w获得。
Sensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and β-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or β-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea. The online version contains supplementary material available at 10.1007/s00441-021-03493-w.
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影响因子：
16.2
作者：
Mizutari K;Fujioka M;Hosoya M;Bramhall N;Okano HJ;Okano H;Edge AS
通讯作者：
Edge AS
影响因子：
4.4
作者：
Hawkins, R. David;Helms, Cynthia A.;Lovett, Michael
通讯作者：
Lovett, Michael
DOI：
10.1002/wdev.302
发表时间：
2018-01
期刊：
Wiley interdisciplinary reviews. Developmental biology
影响因子：
--
作者：
Ohta S;Schoenwolf GC
通讯作者：
Schoenwolf GC
影响因子：
4.3
作者：
Qian, Cuijuan;Liu, Fuqiang;Yao, Jun
通讯作者：
Yao, Jun
DOI：
10.1523/jneurosci.2057-11.2011
发表时间：
2011-10-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lin V;Golub JS;Nguyen TB;Hume CR;Oesterle EC;Stone JS
通讯作者：
Stone JS