Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Cell Biology & Neuroscience, Rutgers University, Nelson Labs D250 604 Allison Rd., Piscataway, NJ 08854, USA; Stem Cell Research Center and Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
Hear Res. 2023 Sep 1;436:108813. doi: 10.1016/j.heares.2023.108813. Epub 2023 May 30.
Loss of spiral ganglion neurons (SGNs) in the cochlea causes hearing loss. Understanding the mechanisms of cell fate transition accelerates efforts that employ directed differentiation and lineage conversion to repopulate lost SGNs. Proposed strategies to regenerate SGNs rely on altering cell fate by activating transcriptional regulatory networks, but repressing networks for alternative cell lineages is also essential. Epigenomic changes during cell fate transitions suggest that CHD4 represses gene expression by altering the chromatin status. Despite limited direct investigations, human genetic studies implicate CHD4 function in the inner ear. The possibility of CHD4 in suppressing alternative cell fates to promote inner ear regeneration is discussed.
耳蜗中的螺旋神经节神经元(SGNs)的丧失会导致听力损失。了解细胞命运转变的机制可以加速利用定向分化和谱系转换来重新填充丢失的 SGN 的努力。再生 SGN 的拟议策略依赖于通过激活转录调控网络来改变细胞命运,但抑制替代细胞谱系的网络也是必不可少的。细胞命运转变过程中的表观遗传变化表明,CHD4 通过改变染色质状态来抑制基因表达。尽管直接研究有限,但人类遗传学研究表明 CHD4 在内耳中的功能。讨论了 CHD4 抑制替代细胞命运以促进内耳再生的可能性。