Liu Li-Man, Zhao Li-Ping, Wu Ling-Jie, Guo Luo, Li Wen-Yan, Chen Yan
ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, Fudan University Shanghai 200031, China.
NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai 200031, China.
Am J Stem Cells. 2020 Feb 15;9(1):1-15. eCollection 2020.
Postnatal mammalian cochlear hair cells (HCs) can be regenerated by direct transdifferentiation or by mitotic regeneration from supporting cells through many pathways, including Atoh1, Wnt, Hedgehog and Notch signaling. However, most new HCs are immature HCs. In this study we used RNA-Seq analysis to compare the differences between the transcriptomes of overexpression-induced new HCs and the native HCs, and to define the factors that might help to promote the maturation of new HCs. As expected, we found -induced new HCs had obvious HC characteristics as demonstrated by the expression of HC markers such as and Myosin VIIA (Myo7a). However, -induced new HCs had significantly lower expression of genes that are related to HC function such as Slc26a5 (), and . We found that genes related to HC cell differentiation and maturation (, , , , , , , , etc.) had significantly lower expression levels in new HCs compared to native HCs. In conclusion, we found a set of genes that might regulate the differentiation and maturation of new HCs, and these genes might serve as potential new therapeutic targets for functional HC regeneration and hearing recovery.
出生后的哺乳动物耳蜗毛细胞(HCs)可通过直接转分化或通过支持细胞经有丝分裂再生,再生途径包括Atoh1、Wnt、Hedgehog和Notch信号通路等多种。然而,大多数新生HCs是未成熟的HCs。在本研究中,我们使用RNA测序分析来比较过表达诱导产生的新生HCs与天然HCs转录组之间的差异,并确定可能有助于促进新生HCs成熟的因素。正如预期的那样,我们发现过表达诱导产生的新生HCs具有明显的HC特征,如通过HC标记物如和肌球蛋白VIIA(Myo7a)的表达所证明。然而,过表达诱导产生的新生HCs中与HC功能相关的基因如Slc26a5()、和的表达显著较低。我们发现,与HC细胞分化和成熟相关的基因(、、、、、、、、等)在新生HCs中的表达水平与天然HCs相比显著较低。总之,我们发现了一组可能调节新生HCs分化和成熟的基因,这些基因可能成为功能性HC再生和听力恢复的潜在新治疗靶点。