Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle

Zhang，Yuan1; Zhang，Shasha1; Zhang，Zhonghong2; Dong，Ying1; Ma，Xiangyu1; Qiang，Ruiying1; Chen，Yin3; Gao，Xia3; Zhao，Chunjie1; Chen，Fangyi4; He，Shuangba5; Chai，Renjie1,6,7,8

2020-10-24

10.18632/aging.104009

Aging-US   影响因子和分区

1945-4589

1945-4589

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.

Foxg1 hair cell regeneration Sox9 supporting cells trans-differentiation

SCI

英语

其他

National Key R&D Program of China[2017YFA0103903] ; Strategic Priority Research Program of the Chinese Academy of Science[XDA16010303] ; National Natural Science Foundation of China[81970882][81970892][81700913] ; Natural Science Foundation of Jiangsu Province[BE2019711][BK20190062] ; Jiangsu Provincial Medical Youth Talent of the Project of Invigorating Health Care through Science, Technology and Education[QNRC2016002] ; Fundamental Research Funds for the Central Universities for the Support Program of Zhishan Youth Scholars of Southeast University[2242020R40137]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:000583838700004

IMPACT JOURNALS LLC

2-s2.0-85095861834

Scopus

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.Department of Ophthalmology,Zhongda Hospital,Southeast University,Nanjing,China
3.Department of Otolaryngology Head and Neck Surgery,Affiliated Drum Tower Hospital of Nanjing University Medical School,Jiangsu Provincial Key Medical Discipline (Laboratory),Nanjing,China
4.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,China
5.Department of Otolaryngology Head and Neck,Nanjing Tongren Hospital,School of Medicine,Southeast University,China
6.Co-Innovation Center of Neuroregeneration,Nantong University,Nantong,China
7.Institute for Stem Cell and Regeneration,Chinese Academy of Science,China
8.Beijing Key Laboratory of Neural Regeneration and Repair,Capital Medical University,China

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.

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),19834-19851.

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.