Ectopic hair cell-like cell induction by Math1 mainly involves direct transdifferentiation in neonatal mammalian cochlea

Ectopic hair cell-like cell induction by Math1 mainly involves direct transdifferentiation in neonatal mammalian cochlea
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Math1诱导异位毛细胞样细胞主要涉及新生哺乳动物耳蜗的直接转分化

DOI:
10.1016/j.neulet.2013.04.053
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发表时间:
2013-08-09
影响因子:
2.5
通讯作者:
Chi, Fanglu
Chi, Fanglu
中科院分区:
医学4区
文献类型:
--
作者:
Yang, Juanmei;Cong, Ning;Chi, Fanglu

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Math 1,也称为Atoh 1,是一种基本的螺旋-环-螺旋转录因子,在毛细胞(HC)发育中起关键作用。以往的研究报道,Math 1基因转移可以诱导产生异位毛细胞样细胞在体外和体内。在这里,我们专注于异位毛细胞样细胞分化的机制与人类腺病毒血清型5(Ad 5)载体编码Math 1和报告基因EGFP的细胞在耳蜗外侧上皮嵴(LER)。在Ad 5-EGFP-Math 1感染的LER中,可以检测到毛细胞样细胞。不同时间点的5 '-溴-2'脱氧尿苷(BrdU)掺入试验结果表明,LER细胞具有较高的增殖潜力,但不能自发转分化为毛细胞。当Math 1表达后BrdU掺入发生时,几乎所有Math 1诱导的毛细胞样细胞均为BrdU阴性。结论:Math 1诱导LER细胞向毛细胞样细胞的分化主要是直接转分化,而不是LER细胞的有丝分裂或新生毛细胞样细胞。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Math1, also known as Atoh1, is a basic helix-loop-helix transcription factor that plays a key role in hair cells (HCs) development. Previous studies have reported that Math1 gene transfer could induce the production of ectopic hair cell-like cells both in vitro and in vivo. Here, we focused on the mechanism of ectopic hair cell-like cellular differentiation from cells in the lateral epithelial ridge (LER) of cochlea with a human adenovirus serotype 5 (Ad5) vector encoding both Math1 and the reporter gene EGFP. Within the Ad5-EGFP-Math1 infection, hair-cell like cells could be detected in the LER. 5'-Bromo-2' deoxyuridine (BrdU) incorporation test results at different time points suggested that LER cells possessed high potential to proliferation, but they could not transdifferentiate into hair cells spontaneously. Almost all of Math1 induced hair cell-like cells were BrdU negative when BrdU incorporation occurred after Math1 expression. In conclusion, Math1 induced hair cell-like cells from LER cells mainly underwent direct trans-differentiation instead of mitosis of LER cells or newly hair cell-like cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.