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Updated: Oct 20, 2025
Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells
Published on: January 2, 2016
High-throughput screening on cochlear organoids identifies VEGFR-MEK-TGFB1 signaling promoting hair cell
Qing Liu1, Linqing Zhang1, Min-Sheng Zhu1
1MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing 210032, China.
Abstract:
Hair cell degeneration is a major cause of sensorineural hearing loss. Hair cells in mammalian cochlea do not spontaneously regenerate, posing a great challenge for restoration of hearing. Here, we establish a robust, high-throughput cochlear organoid platform that facilitates 3D expansion of cochlear progenitor cells and differentiation of hair cells in a temporally regulated manner. High-throughput screening of the FDA-approved drug library identified regorafenib, a VEGFR inhibitor, as a potent small molecule for hair cell differentiation. Regorafenib also promotes reprogramming and maturation of hair cells in both normal and neomycin-damaged cochlear explants. Mechanistically, inhibition of VEGFR suppresses TGFB1 expression via the MEK pathway and TGFB1 downregulation directly mediates the effect of regorafenib on hair cell reprogramming. Our study not only demonstrates the power of a cochlear organoid platform in high-throughput analyses of hair cell physiology but also highlights VEGFR-MEK-TGFB1 signaling crosstalk as a potential target for hair cell regeneration and hearing restoration.
