Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.
Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.
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DOI：
10.3389/fncel.2021.660748
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发表时间：
2021
影响因子：
5.3
通讯作者：
Groves AK
中科院分区：
文献类型：
--
作者：
Iyer AA;Groves AK
非哺乳类脊椎动物可以通过触发邻近支持细胞的再生来自然恢复它们的听觉和前庭毛细胞。转录因子ATOH 1是内耳毛细胞发育和再生的关键调节因子。毛细胞死亡后，支持细胞上调ATOH 1并产生新的毛细胞。然而，在成熟的哺乳动物耳蜗中，毛细胞的这种自然再生基本上是不存在的。转录因子重编程已用于许多组织，将一种细胞类型转化为另一种细胞类型，长期希望实现组织再生。重编程转录因子通过改变靶细胞中的转录组和表观遗传景观来起作用，从而导致所需细胞类型的命运改变。几项研究表明，ATOH 1能够将耳蜗非感觉组织重新编程为类似于年轻动物毛细胞的细胞。然而，ATOH 1的重编程能力随着年龄的增长而丧失，这意味着单个毛细胞特异性转录因子的效力可能会随着时间的推移而降低或丧失，其机制尚不清楚。为了避免这一点，关键毛细胞转录因子的组合已被用于促进老年动物毛细胞再生。在这篇综述中，我们总结了最近的研究结果，已经确定和研究这些重编程因子组合的毛细胞再生。最后，我们讨论了从这些发现中出现的重要问题，特别是在未来使用重编程因子恢复人类听力的治疗策略的可行性。
Non-mammalian vertebrates can restore their auditory and vestibular hair cells naturally by triggering the regeneration of adjacent supporting cells. The transcription factor ATOH1 is a key regulator of hair cell development and regeneration in the inner ear. Following the death of hair cells, supporting cells upregulate ATOH1 and give rise to new hair cells. However, in the mature mammalian cochlea, such natural regeneration of hair cells is largely absent. Transcription factor reprogramming has been used in many tissues to convert one cell type into another, with the long-term hope of achieving tissue regeneration. Reprogramming transcription factors work by altering the transcriptomic and epigenetic landscapes in a target cell, resulting in a fate change to the desired cell type. Several studies have shown that ATOH1 is capable of reprogramming cochlear non-sensory tissue into cells resembling hair cells in young animals. However, the reprogramming ability of ATOH1 is lost with age, implying that the potency of individual hair cell-specific transcription factors may be reduced or lost over time by mechanisms that are still not clear. To circumvent this, combinations of key hair cell transcription factors have been used to promote hair cell regeneration in older animals. In this review, we summarize recent findings that have identified and studied these reprogramming factor combinations for hair cell regeneration. Finally, we discuss the important questions that emerge from these findings, particularly the feasibility of therapeutic strategies using reprogramming factors to restore human hearing in the future.
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影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
DOI：
10.1073/pnas.97.22.11722
发表时间：
2000-10-24
影响因子：
11.1
作者：
Baird, RA;Burton, MD;Naeger, RA
通讯作者：
Naeger, RA
影响因子：
8.8
作者：
Barbagiovanni G;Germain PL;Zech M;Atashpaz S;Lo Riso P;D'Antonio-Chronowska A;Tenderini E;Caiazzo M;Boesch S;Jech R;Haslinger B;Broccoli V;Stewart AF;Winkelmann J;Testa G
通讯作者：
Testa G
影响因子：
2.5
作者：
Cafaro, Jon;Lee, Gi Soo;Stone, Jennifer S.
通讯作者：
Stone, Jennifer S.
影响因子：
2.4
作者：
Basch ML;Brown RM 2nd;Jen HI;Groves AK
通讯作者：
Groves AK