Simultaneous gentamicin-mediated damage and Atoh1 overexpression promotes hair cell regeneration in the neonatal mouse utricle.
Simultaneous gentamicin-mediated damage and Atoh1 overexpression promotes hair cell regeneration in the neonatal mouse utricle.
复制标题
同时庆大霉素介导的损伤和 Atoh1 过度表达可促进新生小鼠椭圆囊中的毛细胞再生。
DOI：
10.1016/j.yexcr.2020.112395
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Ren Dongdong
中科院分区：
文献类型：
--
作者：
Qian Xiaoqing;Ma Rui;Wang Xinwei;Xu Xinda;Yang Juanmei;Chi Fanglu;Ren Dongdong
前庭上皮的毛细胞损失会导致平衡功能障碍。当前的前庭疾病治疗方案是有限的。损伤或ATOH1过表达后，毛细胞的替代迅速发生在哺乳动物的肾上腺中，这表明一种有希望的诱导前庭毛细胞再生的方法。在这项研究中，我们同时应用了庆大霉素介导的毛细胞消融和ATOH1过表达来诱导新生儿的乳细胞造成细胞的形成。我们确认I型毛细胞是庆大霉素的主要靶标。此外，损伤和ATOH1过表达通过可靠的病毒转染及时有效地促进了毛细胞再生。毛细胞在非感官区域中具有II型特征的再生和I/II型特征。异位区域中感觉区域中的罕见EDU+/肌动蛋白7a+细胞以及可鲁棒的EDU+/肌动蛋白7a+信号表明，辅助细胞的转变以及在异位区域中非感官上皮细胞的有丝分裂和分化是再生毛细胞的来源。不同的再生模式因素和异位区域表明前庭非感官上皮的可塑性可塑性，从而产生更发达的毛细胞亚型，从而提供了有希望的干细胞样毛细胞来源。这些发现表明，同时引起损伤和过表达ATOH1会促进毛细胞再生功效和成熟度，从而扩展了对新生儿前庭器官异位可塑性的理解。
Loss of hair cells from vestibular epithelium results in balance dysfunction. The current therapeutic regimen for vestibular diseases is limited. Upon injury or Atoh1 overexpression, hair cell replacement occurs rapidly in the mammalian utricle, suggesting a promising approach to induce vestibular hair cell regeneration. In this study, we applied simultaneous gentamicin-mediated hair cell ablation and Atoh1 overexpression to induce neonatal utricular hair cell formationin vitro. We confirmed that type I hair cells were the primary targets of gentamicin. Furthermore, injury and Atoh1 overexpression promoted hair cell regeneration in a timely and efficient manner through robust viral transfection. Hair cells regenerated with type II characteristics in the striola and type I/II characteristics in non-sensory regions. Rare EdU+/myosin7a+cells in sensory regions and robust EdU+/myosin7a+signals in ectopic regions indicate that transdifferentiation of supporting cellsin situ, and mitosis and differentiation of non-sensory epithelial cells in ectopic regions, are sources of regenerative hair cells. Distinct regeneration patterns inin situand ectopic regions suggested robust plasticity of vestibular non-sensory epithelium, generating more developed hair cell subtypes and thus providing a promising stem cell-like source of hair cells. These findings suggest that simultaneously causing injury and overexpressing Atoh1 promotes hair cell regeneration efficacy and maturity, thus expanding the understanding of ectopic plasticity in neonatal vestibular organs.