Intracellular Regulome Variability Along the Organ of Corti: Evidence, Approaches, Challenges, and Perspective.
Intracellular Regulome Variability Along the Organ of Corti: Evidence, Approaches, Challenges, and Perspective.
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DOI：
10.3389/fgene.2018.00156
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发表时间：
2018
影响因子：
3.7
通讯作者：
Fritzsch B
中科院分区：
文献类型：
--
作者：
Booth KT;Azaiez H;Jahan I;Smith RJH;Fritzsch B
哺乳动物的听觉器官是由两种类型的毛细胞（HC）组成的规则阵列，周围有六种类型的支持细胞。沿着音调轴，这种保守的放射状排列的细胞类型显示出纵向变化，以增强基底膜的调谐特性。我们目前的证据支持的假设，定量的局部基因表达谱的变化是负责全球基因操作的局部细胞反应。随着下一代测序技术的出现和前所未有的一系列技术在单细胞水平上提供高通量分析，转录组学将成为增强我们对内耳理解的常用工具。我们提供了一个概述的方法和里程碑式的研究进行到目前为止，以分析单细胞变异的Corti器官，并讨论目前的局限性。接下来，我们将概述内耳中已知的调节机制的复杂性。这些机制在转录、RNA剪接、mRNA调节和翻译水平上在时间和空间上受到严格调控。要了解内耳中复杂的调控机制，需要使用互补的方法，最有可能的是将转录组学、蛋白质组学和表观基因组学技术结合起来的组合策略。我们强调这些数据，结合最近对分子细胞转化的见解，可以促进恢复丢失的毛细胞的尝试。
The mammalian hearing organ is a regular array of two types of hair cells (HCs) surrounded by six types of supporting cells. Along the tonotopic axis, this conserved radial array of cell types shows longitudinal variations to enhance the tuning properties of basilar membrane. We present the current evidence supporting the hypothesis that quantitative local variations in gene expression profiles are responsible for local cell responses to global gene manipulations. With the advent of next generation sequencing and the unprecedented array of technologies offering high throughput analyses at the single cell level, transcriptomics will become a common tool to enhance our understanding of the inner ear. We provide an overview of the approaches and landmark studies undertaken to date to analyze single cell variations in the organ of Corti and discuss the current limitations. We next provide an overview of the complexity of known regulatory mechanisms in the inner ear. These mechanisms are tightly regulated temporally and spatially at the transcription, RNA-splicing, mRNA-regulation, and translation levels. Understanding the intricacies of regulatory mechanisms at play in the inner ear will require the use of complementary approaches, and most probably, a combinatorial strategy coupling transcriptomics, proteomics, and epigenomics technologies. We highlight how these data, in conjunction with recent insights into molecular cell transformation, can advance attempts to restore lost hair cells.
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影响因子：
16.6
作者：
Burns JC;Kelly MC;Hoa M;Morell RJ;Kelley MW
通讯作者：
Kelley MW
影响因子：
11.1
作者：
Bonasio R;Shiekhattar R
通讯作者：
Shiekhattar R
影响因子：
3.7
作者：
Elkan-Miller T;Ulitsky I;Hertzano R;Rudnicki A;Dror AA;Lenz DR;Elkon R;Irmler M;Beckers J;Shamir R;Avraham KB
通讯作者：
Avraham KB
影响因子：
64.5
作者：
Durruthy-Durruthy R;Gottlieb A;Hartman BH;Waldhaus J;Laske RD;Altman R;Heller S
通讯作者：
Heller S
DOI：
10.1016/j.molbrainres.2004.10.001
发表时间：
2005-01-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Cristobal, R;Wackym, PA;Popper, P
通讯作者：
Popper, P