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首页> 外文期刊>Hearing Research: An International Journal >Transcriptomic analysis of chicken cochleae after gentamicin damage and the involvement of four signaling pathways (Notch, FGF, Wnt and BMP) in hair cell regeneration
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Transcriptomic analysis of chicken cochleae after gentamicin damage and the involvement of four signaling pathways (Notch, FGF, Wnt and BMP) in hair cell regeneration

机译:庆大霉素损伤后鸡耳蛋白的转录组分分析及四种信号通路(Notch,FGF,WNT和BMP)在毛细胞再生中的累积

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Unlike mammalian hair cells, which are essentially unable to regenerate after damage, avian hair cells have a robust capacity for regeneration. The prerequisite for understanding the above difference is knowing the genetic programming of avian hair cell regeneration. Although the major processes have been known, the precise molecular signaling that induces regeneration remains unclear. To address this issue, we performed a high-throughput transcriptomic analysis of gene expression during hair cell regeneration in the chick cochlea after antibiotic injury in vivo. A total of 16,588 genes were found to be expressed in the cochlea, of which about 1000 genes were differentially expressed among the four groups studied, i.e., 2 days (d) or 3d post-treatment with gentamicin or physiological saline. The differentially expressed genes were distributed across approximately one hundred signaling pathways, including the Notch, MAPK (FGF), Wnt and TGF-beta (BMP) pathways that have been shown to play important roles in embryonic development. Some differentially expressed genes (2-3 in each pathway) were further verified by qRT-PCR. After blocking Notch, FGF or BMP signaling, the number of regenerating hair cells and mitotic supporting cells increased. However, the opposite effect was observed after suppressing the Wnt pathway or enhancing BMP signaling. To our knowledge, the present study provided a relatively complete dataset of candidate genes and signaling pathways most likely involved in hair cell regeneration and should be a useful start in deciphering the genetic circuitry for inducing hair cell regeneration in the chick cochlea. (C) 2018 Elsevier B.V. All rights reserved.
机译:与哺乳动物的毛发细胞不同,损伤后基本上无法再生,禽毛细胞具有对再生的稳健能力。理解上述差异的先决条件是了解禽毛细胞再生的遗传编程。虽然已知主要方法,但诱导再生的精确分子信号仍然不清楚。为了解决这个问题,我们在体内抗生素损伤后鸡耳耳蜗在鸡耳耳蜗中的基因表达进行了高通量转录组分析。发现总共16,588个基因在耳蜗中表达,其中约1000个基因在研究的四个组中差异表达,即2天(D)或用庆大霉素或生理盐水进行后处理。差异表达的基因分布在大约一百个信令途径上,包括凹口,MAPK(FGF),WNT和TGF-β(BMP)途径,该途径已被证明在胚胎发育中起重要作用。通过QRT-PCR进一步验证一些差异表达的基因(每种途径中的2-3)。在阻断凹口,FGF或BMP信号传导后,再生毛细胞的数量和有丝分子支持细胞的数量增加。然而,在抑制WNT途径或增强BMP信号传导后观察到相反的效果。据我们所知,本研究提供了相对完整的候选基因数据集和最可能参与毛细胞再生的信号传导途径,并且应该是解密遗传电路的有用开始,用于诱导小鸡耳蜗中的头发细胞再生。 (c)2018 Elsevier B.v.保留所有权利。

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