MOE Key Laboratory for Developmental Genes and Human Disease, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
Department of Ophthalmology, Zhongda Hospital, Southeast University, Nanjing, China.
Aging (Albany NY). 2020 Oct 24;12(20):19834-19851. doi: 10.18632/aging.104009.
Foxg1 plays important roles in regeneration of hair cell (HC) in the cochlea of neonatal mouse. Here, we used Sox9-CreER to knock down in supporting cells (SCs) in the utricle in order to investigate the role of Foxg1 in HC regeneration in the utricle. We found Sox9 an ideal marker of utricle SCs and bred Sox9Foxg1 mice to conditionally knock down in utricular SCs. Conditional knockdown (cKD) of in SCs at postnatal day one (P01) led to increased number of HCs at P08. These regenerated HCs had normal characteristics, and could survive to at least P30. Lineage tracing showed that a significant portion of newly regenerated HCs originated from SCs in cKD mice compared to the mice subjected to the same treatment, which suggested SCs trans-differentiate into HCs in the cKD mouse utricle. After neomycin treatment , more HCs were observed in cKD mice utricle compared to the control group. Together, these results suggest that cKD in utricular SCs may promote HC regeneration by inducing trans-differentiation of SCs. This research therefore provides theoretical basis for the effects of Foxg1 in trans-differentiation of SCs and regeneration of HCs in the mouse utricle.
Foxg1 在新生小鼠耳蜗毛细胞（HC）的再生中发挥重要作用。在这里，我们使用 Sox9-CreER 敲低了前庭中的支持细胞（SCs）中的 Foxg1，以研究 Foxg1 在前庭 HC 再生中的作用。我们发现 Sox9 是前庭 SCs 的理想标志物，并繁殖了 Sox9Foxg1 小鼠以条件敲低前庭 SCs 中的 Foxg1。在出生后第 1 天（P01）条件敲低 SCs 中的 Foxg1 导致 P08 时 HC 数量增加。这些再生的 HC 具有正常的特征，并且至少可以存活到 P30。谱系追踪表明，与接受相同处理的小鼠相比，在 Foxg1 条件敲低的小鼠中，相当一部分新再生的 HC 源自 Foxg1 条件敲低的小鼠的 SCs，这表明在 Foxg1 条件敲低的小鼠前庭中 SCs 转分化为 HC。在用新霉素处理后，Foxg1 条件敲低的小鼠前庭中观察到更多的 HC。综上所述，这些结果表明，在 Foxg1 条件敲低的前庭 SCs 中可能通过诱导 SCs 的转分化来促进 HC 的再生。因此，这项研究为 Foxg1 在 SCs 转分化和小鼠前庭 HC 再生中的作用提供了理论依据。
