Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea

doi:10.1016/j.engreg.2023.04.003

科研成果详情

题名	Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea
作者	Zhang, Liyan 1; Qi, Jieyu 1; Fang, Yuan 1; Tan, Fangzhi 1; Zhou, Yinyi 1; Zhang, Ziyu 1; Sun, Qiuhan 1; Li, Nianci 1; Huang, Yideng2; Sun, Jingwu 3; Chai, Renjie 1,4,5,6,7
发表日期	2023-09
发表期刊	Engineered Regeneration 影响因子和分区
语种	英语
原始文献类型	Journal article (JA) ; Article
关键词	Audition Damage detection Mammals Molecular biology Viruses AAV Cell divisions Cell regeneration Cochlea Hair cell regeneration Hair cells Hearing loss Inner ear Organoids Ras association domain family member 2 Organoid Rassf2
摘要	Sensory hair cells are responsible for detecting and transmitting sound in the inner ear, and damage to HCs leads to hearing loss. HCs do not regenerate spontaneously in adult mammals, which makes the hearing loss permanent. However, hair cells and supporting cells have the same precursors in the inner ear, and in newborn mice, the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells. Here, we demonstrate the role of the Ras association domain family member 2 (Rassf2) in supporting cell to hair cell trans-differentiation in the inner ear. Using the AAV vector (AAV-ie) to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids. Also, AAV-Rassf2 enhanced the regenerative ability of Lgr5+ SCs in the postnatal cochlea without impairing hearing, and this might due to the modulation of the Wnt, Hedgehog and Notch signaling pathways. Furthermore, AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model. In summary, our results suggest that Rassf2 is a key component in HC regenerative repair, and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair. © 2023
资助项目	Guangdong Academy of Medical Sciences[YKY-KF202201];Key Program of Zhejiang Provincial Natural Science Foundation of China[LZ22H130001];National Natural Science Foundation of China[81970882,82000984,82030029,82171146,92149304];China Postdoctoral Science Foundation[2020M681468];Fudan University[SKLGE-2104];Science and Technology Department of Sichuan Province[2021YFS0371];China National Postdoctoral Program for Innovative Talents[BX20200082];National Key Research and Development Program of China[2020YFA0112503,2020YFA0113600,2021YFA1101300,2021YFA1101800];Shenzhen Fundamental Research Program[JCYJ20190814093401920,JCYJ20210324125608022];
出版者	KeAi Communications Co.
ISSN	2666-1381
EISSN	2666-1381
卷号	4 期号:3 页码:304-315
DOI	10.1016/j.engreg.2023.04.003
收录类别	EI ; SCOPUS
EI入藏号	20240615515317
EI主题词	Cell proliferation
EI分类号	461.4 Ergonomics and Human Factors Engineering ; 461.9 Biology ; 941.1 Acoustical Instruments
URL	查看原文
SCOPUSEID	2-s2.0-85153799529
通讯作者地址	[Qi, Jieyu]State Key Laboratory of Digital Medical Engineering,Department of Otolaryngology Head and Neck Surgery,Zhongda Hospital,School of Life Sciences and Technology,Advanced Institute for Life and Health,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,Southeast University,Nanjing,210096,China
Scopus学科分类	Medicine (miscellaneous);Biomaterials;Biomedical Engineering
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210448
专题	附属第一医院
通讯作者	Qi, Jieyu
作者单位	1.State Key Laboratory of Digital Medical Engineering,Department of Otolaryngology Head and Neck Surgery,Zhongda Hospital,School of Life Sciences and Technology,Advanced Institute for Life and Health,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,Southeast University,Nanjing,210096,China; 2.Department of Otolaryngology,The First Affiliated Hospital of Wenzhou Medical University,Village ShangCai, Ouhai District,Wenzhou city,325000,China; 3.Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of University of Science and Technology of China,China; 4.Department of Otolaryngology Head and Neck Surgery,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu,China; 5.Co-Innovation Center of Neuroregeneration,Nantong University,Nantong,226001,China; 6.Institute for Stem Cell and Regeneration,Chinese Academy of Science,Beijing,China; 7.Beijing Key Laboratory of Neural Regeneration and Repair,Capital Medical University,Beijing,100069,China
推荐引用方式 GB/T 7714	Zhang, Liyan,Qi, Jieyu,Fang, Yuan,et al. Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea[J]. Engineered Regeneration,2023,4(3):304-315.
APA	Zhang, Liyan., Qi, Jieyu., Fang, Yuan., Tan, Fangzhi., Zhou, Yinyi., ... & Chai, Renjie. (2023). Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea. Engineered Regeneration, 4(3), 304-315.
MLA	Zhang, Liyan,et al."Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea".Engineered Regeneration 4.3(2023):304-315.