机构：[1]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[2]Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China[3]Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China[4]Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China[5]Department of Ophthalmology, Zhongda Hospital, Southeast University, Nanjing, China[6]Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline Laboratory, Nanjing, China[7]Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China深圳市康宁医院深圳医学信息中心[8]Department of Otolaryngology Head and Neck, Nanjing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China
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.
基金：
This work was supported by grants from the National
Key R&D Program of China (No. 2017YFA0103903),
the Strategic Priority Research Program of the Chinese
Academy of Science (XDA16010303), the National
Natural Science Foundation of China (Nos. 81970882,
81970892, 81700913), the Natural Science Foundation
of Jiangsu Province (BE2019711, BK20190062), the
Jiangsu Provincial Medical Youth Talent of the Project
of Invigorating Health Care through Science,
Technology and Education (QNRC2016002), and the
Fundamental Research Funds for the Central
Universities for the Support Program of Zhishan Youth
Scholars of Southeast University (2242020R40137).
第一作者机构：[1]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
共同第一作者：
通讯作者：
通讯机构：[1]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[2]Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China[3]Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China[4]Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Zhang Yuan,Zhang Shasha,Zhang Zhonghong,et al.Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle.[J].AGING-US.2020,12(20):19834-19851.doi:10.18632/aging.104009.
APA：
Zhang Yuan,Zhang Shasha,Zhang Zhonghong,Dong Ying,Ma Xiangyu...&Chai Renjie.(2020).Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle..AGING-US,12,(20)
MLA：
Zhang Yuan,et al."Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle.".AGING-US 12..20(2020):19834-19851
