RT Journal Article
SR Electronic
T1 Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.21.427665
DO 10.1101/2021.01.21.427665
A1 Suhong Sun
A1 Shuting Li
A1 Zhengnan Luo
A1 Minhui Ren
A1 Shunji He
A1 Guangqin Wang
A1 Zhiyong Liu
YR 2021
UL http://biorxiv.org/content/early/2021/01/21/2021.01.21.427665.abstract
AB Mammalian cochlear outer hair cells (OHCs) are essential for hearing. OHC degeneration causes severe hearing impairment. Previous attempts of regenerating new OHCs from cochlear supporting cells (SCs) had yielded cells lacking Prestin, a key motor protein for OHC function. Thus, regeneration of Prestin+ OHCs remains a challenge for repairing OHC damage in vivo. Here, we reported that successful in vivo conversion of adult cochlear SCs into Prestin+ OHC-like cells could be achieved by simultaneous expression of Atoh1 and Ikzf2, two key transcriptional factors necessary for OHC development. New OHC-like cells exhibited upregulation of hundreds of OHC genes and downregulation of SC genes. Single cell transcriptomic analysis demonstrated that the differentiation status of these OHC-like cells was much more advanced than previously achieved. Thus, we have established an efficient approach to promote regeneration of Prestin+ OHCs and paved the way for repairing damaged cochlea in vivo via transdifferentiation of SCs.