Rps14 upregulation promotes inner ear progenitor proliferation and hair cell regeneration in the neonatal mouse cochlea

Author:

Xu Changling123,Qi Jieyu4,Hu Xiaojie4,Zhang Liyan4,Sun Qiuhan4,Li Nianci4,Chen Xin4,Guo Fangfang5,Wu Peina67,Shi Yi123,Chai Renjie4891011ORCID

Affiliation:

1. Health Management Center Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China Chengdu China

2. Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu China

3. Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital Chengdu Sichuan China

4. State Key Laboratory of Bioelectronics, 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

5. Department of Plastic and Reconstruction surgery Zhongda Hospital, Southeast University 87 Dingjiaqiao Street, Nanjing Jiangsu Province China

6. Department of Otolaryngology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou 510080 China

7. School of Medicine South China University of Technology Guangzhou 510006 China

8. Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China Chengdu China

9. Co‐Innovation Center of Neuroregeneration, Nantong University Nantong 226001 China

10. Institute for Stem Cell and Regeneration, Chinese Academy of Science Beijing China

11. Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University 100069 Beijing China

Abstract

AbstractSensorineural hearing loss a result from hair cell damage, which is irreversible in mammals owing to the lack of hair cell regeneration, but recent researches have shown that Lgr5+ supporting cells are progenitors capable of regenerating hair cells. RPS14 (ribosomal protein S14) is a 40S ribosomal subunit component and is associated with erythrocyte differentiation, and in this study, we used a novel adeno‐associated virus‐inner ear system to upregulate Rps14 expression in cultured hair cell progenitors and observed an enhancement on their ability to proliferate and differentiate into hair cells. Similarly, Rps14 overexpression in the mice cochlea could promote supporting cells proliferation by activating the Wnt signalling pathway. In addition, over‐expressing Rps14 induced hair cells regeneration in the organ of Corti, and lineage tracing showed that the new hair cells had transformed from Lgr5+ progenitors. In conclusion, our analysis reveals the potential role of Rps14 in driving hair cell regeneration in mammalian.

Funder

China Postdoctoral Science Foundation

Department of Science and Technology of Sichuan Province

Fundamental Research Funds for the Central Universities

National Key Research and Development Program of China

National Natural Science Foundation of China

Shenzhen Fundamental Research Program

Publisher

Wiley

Subject

Cell Biology,General Medicine

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