Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle.
Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle.
复制标题
Sox9 支持细胞中 Foxg1 的敲低会增加新生小鼠椭圆囊中支持细胞向毛细胞的转分化。
DOI：
10.18632/aging.104009
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发表时间：
2020-10-24
期刊：
影响因子：
--
通讯作者：
Chai R
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhang S;Zhang Z;Dong Y;Ma X;Qiang R;Chen Y;Gao X;Zhao C;Chen F;He S;Chai R
FOXG1在新生小鼠耳蜗毛细胞(HC)再生中起重要作用。在这里，我们使用Sox9-Creer来敲除椭圆体中支持细胞(SCs)中的FOXG1，以研究FOXG1在椭圆体中HC再生中的作用。我们发现Sox9是椭圆状SCs的理想标记物，并培育了Sox9Creer/+Foxg1loxp/loxP小鼠，有条件地敲除了椭圆状SCs中的FOXG1。在出生后第1天，SCs中FOXG1的条件性基因敲除(CKD)导致Hcs数量在P08增加(P0.01)。这些再生的HCs具有正常的特性，至少可以存活到P30。谱系追踪显示，与相同处理的小鼠相比，FOXG1 CKD小鼠中有很大一部分新再生的HCs来自于SCs，这表明SCs在FOXG1 CKD小鼠的椭圆形中反式分化为HCs。体外新霉素处理后，FOXG1CKD小鼠椭圆体内的HCS较对照组明显增多。综上所述，这些结果提示FOXG1CKD可能通过诱导SCs的转分化来促进HC再生。本研究为FOXG1在小鼠卵圆囊内SCs转分化和HCS再生中的作用提供了理论依据。
Foxg1 plays important roles in regeneration of hair cell (HC) in the cochlea of neonatal mouse. Here, we used Sox9-CreER to knock down Foxg1 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 Sox9CreER/+Foxg1loxp/loxp mice to conditionally knock down Foxg1 in utricular SCs. Conditional knockdown (cKD) of Foxg1 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 Foxg1 cKD mice compared to the mice subjected to the same treatment, which suggested SCs trans-differentiate into HCs in the Foxg1 cKD mouse utricle. After neomycin treatment in vitro, more HCs were observed in Foxg1 cKD mice utricle compared to the control group. Together, these results suggest that Foxg1 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.
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影响因子：
16.6
作者：
Burns JC;Kelly MC;Hoa M;Morell RJ;Kelley MW
通讯作者：
Kelley MW
DOI：
10.1523/jneurosci.6274-11.2012
发表时间：
2012-05-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Burns JC;Cox BC;Thiede BR;Zuo J;Corwin JT
通讯作者：
Corwin JT
影响因子：
3.7
作者：
Burns JC;Yoo JJ;Atala A;Jackson JD
通讯作者：
Jackson JD
影响因子：
4.6
作者：
Herrera, E;Marcus, R;Mason, C
通讯作者：
Mason, C
影响因子：
2.7
作者：
Fotaki, Vassiliki;Smith, Rowena;Pratt, Thomas;Price, David J.
通讯作者：
Price, David J.