Stepwise Induction of Inner Ear Hair Cells From Mouse Embryonic Fibroblasts via Mesenchymal- to-Epithelial Transition and Formation of Otic Epithelial Cells

Frontiers in Cell and Developmental Biology

Haosong Shi¹  Shan-Kai Yin¹  Hai-Bo Shi¹  Yizhou Quan²  Zhongzhong Ji²  Wei-Qiang Gao²  Qianqian Chen²  Huiming Xu³  Li Wang³  Wang Li³  Yonghui Wang³  Qiong Yang³ 

[1] Department of Otorhinolaryngology, The Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, China;School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China;State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;

关键词: hair cell regeneration;    mesenchymal-to-epithelial transition (MET);    hearing loss;    mouse embryonic fibroblasts;    transdifferentiation;   

DOI  :  10.3389/fcell.2021.672406

来源: DOAJ

【 摘 要 】

Although embryonic stem cells or induced pluripotent stem cells are able to differentiate into inner ear hair cells (HCs), they have drawbacks limiting their clinical application, including a potential risk of tumourigenicity. Direct reprogramming of fibroblasts to inner ear HCs could offer an alternative solution to this problem. Here, we present a stepwise guidance protocol to induce mouse embryonic fibroblasts to differentiate into inner ear HC-like cells (HCLs) via mesenchymal-to-epithelial transition and then acquisition of otic sensory epithelial cell traits by overexpression of three key transcription factors. These induced HCLs express multiple HC-specific proteins, display protrusions reminiscent of ciliary bundle structures, respond to voltage stimulation, form functional mechanotransduction channels, and exhibit a transcriptional profile of HC signature. Together, our work provides a new method to produce functional HCLs in vitro, which may have important implications for studies of HC development, drug discovery, and cell replacement therapy for hearing loss.

【 授权许可】

Unknown