Differential chromatin accessibility, gene expression and mRNA splicing between developing cochlear inner and outer hair cells [RNA-Seq]

The mammalian cochlea has two types of low abundance and highly specialized inner (IHC) and outer (OHC) mechanosensory hair cells. Their malfunction or death are common causes of congenital and acquired deafness. We separately collected developing IHCs and OHCs to identify their mRNAs and chromatin state. We examined their transcriptomes by RNA-seq to reveal differences in gene expression and alternative mRNA splicing. We examined their chromatin conformation by ATAC-seq to reveal open vs closed promoter and enhancer elements. Combining both approaches we find that developing IHCs and OHCs have differentially accessible promoters in differentially expressed genes, differ in both levels of gene expression, extent of mRNA splicing and transcription start sites, and utilize unique promoters and mRNA isoforms absent in other cell types. We provide a resource for the identification of promoter and mRNA isoforms of every gene expressed by IHCs or OHCs. RNA-seq profiling of wild type inner and outer hair cells from neonatal mouse cochlea.

哺乳动物耳蜗中存在两种低丰度且高度特化的机械感觉毛细胞：内毛细胞（Inner Hair Cell，IHC）与外毛细胞（Outer Hair Cell，OHC）。二者的功能异常或死亡是先天性与获得性耳聋的常见致病原因。本研究分别分离获取发育阶段的内毛细胞与外毛细胞，以解析其信使RNA（mRNA）及染色质状态。我们通过RNA测序（RNA-seq）分析其转录组，以揭示基因表达与可变mRNA剪接的差异；借助转座酶可及性测序（ATAC-seq）解析其染色质构象，以明确启动子与增强子元件的开放/闭合状态。结合上述两种分析手段，我们发现发育阶段的内毛细胞与外毛细胞在差异表达基因中存在启动子可及性差异；二者在基因表达水平、mRNA剪接程度及转录起始位点上均有所不同，且各自拥有其他细胞类型中未检测到的独特启动子与mRNA异构体。本研究可为鉴定内毛细胞或外毛细胞所表达的全部基因的启动子与mRNA异构体提供研究资源。本数据集涵盖新生小鼠耳蜗野生型内毛细胞与外毛细胞的RNA测序分析数据。