@ARTICLE{10.3389/fcell.2021.672406, AUTHOR={Yang, Qiong and Shi, Haosong and Quan, Yizhou and Chen, Qianqian and Li, Wang and Wang, Li and Wang, Yonghui and Ji, Zhongzhong and Yin, Shan-Kai and Shi, Hai-Bo and Xu, Huiming and Gao, Wei-Qiang}, TITLE={Stepwise Induction of Inner Ear Hair Cells From Mouse Embryonic Fibroblasts via Mesenchymal- to-Epithelial Transition and Formation of Otic Epithelial Cells}, JOURNAL={Frontiers in Cell and Developmental Biology}, VOLUME={9}, YEAR={2021}, URL={https://www.frontiersin.org/articles/10.3389/fcell.2021.672406}, DOI={10.3389/fcell.2021.672406}, ISSN={2296-634X}, ABSTRACT={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.} }