The Transcriptomics to Proteomics of Hair Cell Regeneration: Looking for a Hair Cell in a Haystack

Abstract

Mature mammals exhibit very limited capacity for regeneration of auditory hair cells, while all non-mammalian vertebrates examined can regenerate them. In an effort to find therapeutic targets for deafness and balance disorders, scientists have examined gene expression patterns in auditory tissues under different developmental and experimental conditions. Microarray technology has allowed the large-scale study of gene expression profiles (transcriptomics) at whole-genome levels, but since mRNA expression does not necessarily correlate with protein expression, other methods, such as microRNA analysis and proteomics, are needed to better understand the process of hair cell regeneration. These technologies and some of the results of them are discussed in this review. Although there is a considerable amount of variability found between studies owing to different species, tissues and treatments, there is some concordance between cellular pathways important for hair cell regeneration. Since gene expression and proteomics data is now commonly submitted to centralized online databases, meta-analyses of these data may provide a better picture of pathways that are common to the process of hair cell regeneration and lead to potential therapeutics. Indeed, some of the proteins found to be regulated in the inner ear of animal models (e.g., IGF-1) have now gone through human clinical trials.

Sensory hair cell death and regeneration in fishes

“…Further, miR-96 can regulate differentiation of cochlear hair cells (Kuhn et al, 2011 ). A more in depth review of miRNAs regulated in vertebrate hair cells is provided elsewhere (Smith and Rajadinakaran, 2013 ).…”

Early growth response protein 1 regulates promoter activity of α-plasma membrane calcium ATPase 2, a major calcium pump in the brain and auditory system

“…Candidates were narrowed down to the following transcription factors: ATOH1, EGR1, GATA3, POU4F3, and USF1. Together these transcription factors are involved in hair cell development and maintenance, synaptic plasticity, regeneration and tissue repair [ 28 – 38 ]. The predicted binding sites for these genes can be found in Fig.…”

Gene expression profiling of the inner ear

“…The number of studies using gene profiling based on microarrays or next‐generation sequencing has increased dramatically over the recent years (Smith & Rajadinakaran, ). These techniques are nowadays commonly used to efficiently analyse the complexity of gene expression levels under different conditions at the tissue‐ or cell type‐specific level.…”

“…Further changes may also occur at the post‐translational level by, for example, protein phosphorylation. Large‐scale proteomic analyses are conducted using two‐dimensional difference gel electrophoresis (2D‐DIGE), antibody microarrays or liquid chromatography coupled with mass spectrometry (Smith & Rajadinakaran, ; Darville & Sokolowski, ). Applying these techniques, several interesting studies have already been conducted, such as defining the proteome of the hair cell's ribbon synapse (Uthaiah & Hudspeth, ) and stereocilia (Shin et al.…”

“…Comparing the (2011) expression profile between the endolymphatic sac and the surrounding dura, 463 specific genes could be identified and were annotated to 29 functional clusters (Friis et al 2011). A recent study in the mouse compared the expression profile of early postnatal cochlear sensory epithelia at P3 and adult age (Figs 3 and 4) with the aim to identify genes that are involved in regeneration or repair (Smeti et al 2012). These properties are present at postnatal stages but completely lost in adult mammals.…”