Expression of Atoh1, Gfi1, and Pou4f3 in the mature cochlea reprograms nonsensory cells into hair cells

被引:10
作者
Mcgovern, Melissa M. [1 ]
Hosamani, Ishwar, V [2 ]
Niu, Yichi [2 ]
Nguyen, Ken Y. [1 ]
Zong, Chenghang [2 ]
Groves, Andrew K. [1 ,2 ]
机构
[1] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
关键词
inner ear; reprogramming; hair cells; cochlea; ATOH1; P27(KIP1); FATE; EPITHELIUM; ORGAN; CORTI;
D O I
10.1073/pnas.2304680121
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate; consequently, loss of hair cells leads to permanent hearing loss. Although nonmammalian vertebrates can regenerate hair cells from neighboring supporting cells, many humans with severe hearing loss lack both hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of nonsensory cells. To determine whether the mature cochlea can produce hair cells in vivo, we reprogrammed nonsensory cells adjacent to the organ of Corti with three hair cell transcription factors: Gfi1, Atoh1, and Pou4f3. We generated numerous hair cell-like cells in nonsensory regions of the cochlea and new hair cells continued to be added over a period of 9 wk. Significantly, cells adjacent to reprogrammed hair cells expressed markers of supporting cells, suggesting that transcription factor reprogramming of nonsensory cochlear cells in adult animals can generate mosaics of sensory cells like those seen in the organ of Corti. Generating such sensory mosaics by reprogramming may represent a potential strategy for hearing restoration in humans.
引用
收藏
页数:11
相关论文
共 47 条
  • [11] POU4F3 pioneer activity enables ATOH1 to drive diverse mechanoreceptor differentiation through a feed-forward epigenetic mechanism
    Yu, Haoze, V
    Tao, Litao
    Llamas, Juan
    Wang, Xizi
    Nguyen, John D.
    Trecek, Talon
    Segil, Neil
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 118 (29)
  • [12] β-Catenin Up-regulates Atoh1 Expression in Neural Progenitor Cells by Interaction with an Atoh1 3′ Enhancer
    Shi, Fuxin
    Cheng, Yen-fu
    Wang, Xiaohui L.
    Edge, Albert S. B.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (01) : 392 - 400
  • [13] Developmental and Functional Hair Cell-Like Cells Induced by Atoh1 Overexpression in the Adult Mammalian Cochlea In Vitro
    Kong, Lingyi
    Xin, Yuan
    Chi, Fanglu
    Chen, Jie
    Yang, Juanmei
    NEURAL PLASTICITY, 2020, 2020
  • [14] The Promoter and Multiple Enhancers of the pou4f3 Gene Regulate Expression in Inner Ear Hair Cells
    Masuda, Masatsugu
    Li, Yan
    Pak, Kwang
    Chavez, Eduardo
    Mullen, Lina
    Ryan, Allen F.
    MOLECULAR NEUROBIOLOGY, 2017, 54 (07) : 5414 - 5426
  • [15] The Promoter and Multiple Enhancers of the pou4f3 Gene Regulate Expression in Inner Ear Hair Cells
    Masatsugu Masuda
    Yan Li
    Kwang Pak
    Eduardo Chavez
    Lina Mullen
    Allen F Ryan
    Molecular Neurobiology, 2017, 54 : 5414 - 5426
  • [16] GFI1 functions to repress neuronal gene expression in the developing inner ear hair cells
    Matern, Maggie S.
    Milon, Beatrice
    Lipford, Erika L.
    McMurray, Mark
    Ogawa, Yoko
    Tkaczuk, Andrew
    Song, Yang
    Elkon, Ran
    Hertzano, Ronna
    DEVELOPMENT, 2020, 147 (17):
  • [17] Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in the mature mouse utricle
    Wang, Tian
    Yang, Tian
    Kedaigle, Amanda
    Pregernig, Gabriela
    McCarthy, Ryan
    Holmes, Ben
    Wu, Xudong
    Becker, Lars
    Pan, Ning
    So, Kathy
    Chen, Leon
    He, Jun
    Mahmoudi, Ahmad
    Negi, Soumya
    Kowalczyk, Monika
    Gibson, Tyler
    Druckenbrod, Noah
    Cheng, Alan G.
    Burns, Joseph
    NATURE COMMUNICATIONS, 2024, 15 (01)
  • [18] Characterization of the Transcriptome of Nascent Hair Cells and Identification of Direct Targets of the Atoh1 Transcription Factor
    Cai, Tiantian
    Jen, Hsin-I
    Kang, Hyojin
    Klisch, Tiemo J.
    Zoghbi, Huda Y.
    Groves, Andrew K.
    JOURNAL OF NEUROSCIENCE, 2015, 35 (14) : 5870 - 5883
  • [19] In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2
    Li, Xiang
    Ren, Minhui
    Gu, Yunpeng
    Zhu, Tong
    Zhang, Yu
    Li, Jie
    Li, Chao
    Wang, Guangqin
    Song, Lei
    Bi, Zhenghong
    Liu, Zhiyong
    DEVELOPMENT, 2023, 150 (24): : 1 - 14
  • [20] Characterization of the transcriptomes of Atoh1-induced hair cells in the mouse cochlea
    Liu, Li-Man
    Zhao, Li-Ping
    Wu, Ling-Jie
    Guo, Luo
    Li, Wen-Yan
    Chen, Yan
    AMERICAN JOURNAL OF STEM CELLS, 2020, 9 (01): : 1 - +