Renewed proliferation in adult mouse cochlea and regeneration of hair cells

Yilai Shu, Wenyan Li, Mingqian Huang, Yi-Zhou Quan, Deborah Scheffer, Chunjie Tian, Yong Tao, Xuezhong Liu, Konrad Hochedlinger, Artur A. Indzhykulian, Zhengmin Wang, Huawei Li and Zheng-Yi Chen ()
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Yilai Shu: Harvard Medical School
Wenyan Li: Harvard Medical School
Mingqian Huang: Harvard Medical School
Yi-Zhou Quan: Harvard Medical School
Deborah Scheffer: Harvard Medical School
Chunjie Tian: Harvard Medical School
Yong Tao: Harvard Medical School
Xuezhong Liu: University of Miami School of Medicine
Konrad Hochedlinger: Massachusetts General Hospital
Artur A. Indzhykulian: Harvard Medical School
Zhengmin Wang: Fudan University
Huawei Li: Fudan University
Zheng-Yi Chen: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract The adult mammalian inner ear lacks the capacity to divide or regenerate. Damage to inner ear generally leads to permanent hearing loss in humans. Here, we present that reprogramming of the adult inner ear induces renewed proliferation and regeneration of inner ear cell types. Co-activation of cell cycle activator Myc and inner ear progenitor gene Notch1 induces robust proliferation of diverse adult cochlear sensory epithelial cell types. Transient MYC and NOTCH activities enable adult supporting cells to respond to transcription factor Atoh1 and efficiently transdifferentiate into hair cell-like cells. Furthermore, we uncover that mTOR pathway participates in MYC/NOTCH-mediated proliferation and regeneration. These regenerated hair cell-like cells take up the styryl dye FM1-43 and are likely to form connections with adult spiral ganglion neurons, supporting that Myc and Notch1 co-activation is sufficient to reprogram fully mature supporting cells to proliferate and regenerate hair cell-like cells in adult mammalian auditory organs.

Date: 2019
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DOI: 10.1038/s41467-019-13157-7

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