• Jingrong Lu, Lingxiang Hu, Bin Ye, Haixia Hu, Yong Tao, Yilai Shu, Hao ChiangDepartment of Otolaryngology, Harvard Medical School, Boston, MA 02115, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA 02114, USA., Vikrant Borse, Mingliang Xiang, Hao Wu, Albert S B Edge, and Fuxin Shi.
• Department of Otolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China.
• Neuroscience. 2019 Dec 1; 422: 146160146-160.

AbstractThe vestibular system of the inner ear contains Type I and Type II hair cells (HCs) generated from sensory progenitor cells; however, little is known about how the HC subtypes are formed. Sox2 (encoding SRY-box 2) is expressed in Type II, but not in Type I, HCs. The present study aimed to investigate the role of SOX2 in cell fate determination in Type I vs. Type II HCs. First, we confirmed that Type I HCs developed from Sox2-expressing cells through lineage tracing of Sox2-positive cells using a CAG-tdTomato reporter mouse crossed with a Sox2-CreER mouse. Then, Sox2 loss of function was induced in HCs, using Sox2flox transgenic mice crossed with a Gfi1-Cre driver mouse. Knockout of Sox2 in HCs increased the number of Type I HCs and decreased the number of Type II HCs, while the total number of HCs and Sox2-positive supporting cells did not change. In addition, the effect of Sox2-knockout persisted into adulthood, resulting in an increased number of Type I HCs. These results demonstrate that SOX2 plays a critical role in the determination of Type II vs. Type I HC fate. The results suggested that Sox2 is a potential target for generating Type I HCs, which may be important for regenerative strategies for balance disorders.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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