<i>Pcolce2</i> overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea
Changling Xu, Liyan Zhang, Yinyi Zhou, Haoliang Du, Jieyu Qi, Fangzhi Tan, Peng Li, Xingliang Gu, Nianci Li, Qiuhan Sun, Ziyu Zhang, Yicheng Lu, Xiaoyun Qian, Busheng Tong, Jiaqiang Sun, Renjie Chai, Yi Shi
Abstract
Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.