John D. Dingell VA Medical Center.
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit.
Curr Opin Otolaryngol Head Neck Surg. 2021 Oct 1;29(5):400-406. doi: 10.1097/MOO.0000000000000752.
To give an overview of recent advances in mammalian auditory hair cell regeneration.
Supporting cells act as progenitors to regenerate hair cells in the prehearing mammalian cochlea but not in the mature cochlea. To overcome this developmental obstacle, manipulation of multiple genes and intracellular pathways has been investigated, which has obtained promising data. This review focuses on recent advances in auditory hair cell regeneration, including synergic gene regulation associated with Atoh1 and Notch signaling, epigenetics, and functional recovery of regenerated hair cells. Co-manipulation of genes critical for hair cell development and cell cycle re-entry, including Atoh1, Isl1, Pou4f3, Gata3, Gfi1, P27kip1, RB, Myc, and Notch-signaling genes, has generated hair cell-like cells in the adult cochlea both in vitro and in vivo. The epigenetic mechanism has been studied in hair cell development and regeneration. Regeneration of hair cell function has a very limited progress, which lacks in-vitro and in-vivo electrophysiology data.
Regeneration of adult auditory hair cells remains a major challenge. Manipulation of multiple genes and pathways together with epigenetic regulation might potentially regenerate functional hair cells in the adult mammalian cochlea.
目的综述：概述哺乳动物听觉毛细胞再生的最新进展。
最新发现：支持细胞作为祖细胞，可在未成熟的哺乳动物耳蜗中再生毛细胞，但不能在成熟的耳蜗中再生。为了克服这一发育障碍，人们研究了多种基因和细胞内途径的操作，这些研究取得了有前景的数据。本文重点介绍了听觉毛细胞再生的最新进展，包括与 Atoh1 和 Notch 信号相关的协同基因调控、表观遗传学以及再生毛细胞的功能恢复。共同操纵对毛细胞发育和细胞周期重新进入至关重要的基因，包括 Atoh1、Isl1、Pou4f3、Gata3、Gfi1、P27kip1、RB、Myc 和 Notch 信号基因，已在体外和体内成年耳蜗中产生了毛细胞样细胞。表观遗传机制已在毛细胞发育和再生中得到研究。毛细胞功能的再生进展非常有限，缺乏体外和体内电生理学数据。
总结：成年听觉毛细胞的再生仍然是一个主要的挑战。多种基因和途径的操作以及表观遗传调控可能有潜力在成年哺乳动物耳蜗中再生功能性毛细胞。
