Abstract：
Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.
摘要：
Atoh1在耳蜗上皮中的过度表达诱导新的毛细胞形成。腺病毒介导的Atoh1过表达的使用主要集中在大鼠较小的上皮脊，并诱导异位毛细胞再生。大鼠耳蜗的感觉区难以转染，因此，在大鼠耳蜗外植体中很少产生新的毛细胞。在含有10％胎牛血清的培养基中培养大鼠耳蜗后，随着支持细胞区域的宽度显着增加，腺病毒成功地感染了感觉区域。编码Atoh1的腺病毒感染感觉区并原位诱导毛细胞形成。联合应用Notch抑制剂DAPT和Atoh1可提高Atoh1的表达水平，降低hes1和hes5的水平，进一步促进毛细胞生成。我们的结果表明，DAPT增强Atoh1活性以促进体外大鼠耳蜗感觉上皮的毛细胞再生。
