在发育中的耳内外毛细胞之间差异化染色质可访问性,基因表达和mRNA剪接
Chuan Zhi Foo1,2, Anne Duggan1, Elizabeth T Bartom3
1Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Journal of the Association for Research in Otolaryngology : JARO
|September 5, 2025
概括
在尾中发育的内外毛细胞表现出不同的基因表达和拼接模式,由染色质可访问性调节. 这项研究为听力和聋的分子基础提供了洞察力.
科学领域:
- 基因组学
- 表观遗传学
- 发育生物学
背景情况:
- 哺乳动物的耳毛细胞,内部 (IHC) 和外部 (OHC),对于听力至关重要.
- 这些细胞的功能障碍或丧失导致先天性和获得性聋.
- 在发育过程中,IHC和OHC具有不同的转录组.
研究的目的:
- 在IHC和OHC发育过程中研究基因表达差异的染色质水平调节.
- 在IHC和OHC之间探索mRNA拼接的差异.
- 确定染色体可访问性的差异是否解释了基因表达的差异.
主要方法:
- 开发小鼠IHC和OHC的大量RNA测序以分析转录组.
- 开发小鼠IHC和OHC的批量ATAC测序以绘制染色质可访问性.
- 对RNA-seq和ATAC-seq数据进行比较分析,以将基因表达与染色质状态联系起来.
主要成果:
- 在开发IHC和OHC的许多差异表达基因的促进者中观察到差异性染色质可访问性.
- 过渡性发育基因和持续成年表达的基因都显示出明显的染色体可访问性.
- 替代的mRNA拼接和转录起点有助于转录组的多样性.
- 耳毛细胞表现出在其他细胞类型中未发现的独特促进体和mRNA异型.
结论:
- 在发育的毛细胞类型中,差异性基因表达是由转录前和后的机制控制的.
- 耳毛细胞中的独特促进体和mRNA异型突显了研究罕见细胞类型转录体和表观体的重要性.
- 为可视化新生儿毛细胞中的基因促进物和mRNA异型提供了一个公开的资源.
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