PMC:3886832 / 15132-18623 JSONTXT

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Cell- and Tissue-Specific Transcript Profiling\nOne of the first steps to understanding pathways involved in hair cell regeneration is to separate genes that are expressed in auditory sensory tissues compared to other reference tissues. One of the first array studies to be applied to inner ear tissue compared regions of the rat cochlea to the cochlear nucleus, inferior colliculus and hippocampus [58]. Greater differences in gene expression were found between the cochlea and the central nervous system regions than between the central auditory regions and the hippocampus, showing that gene expression patterns in peripheral and central nervous tissues differ. Genes that were expressed at higher levels in the cochlea included insulin-like growth factor binding proteins, matrix metalloproteinases and tissue inhibitors of metalloproteinases [58].\nWithin the inner ear itself, gene expression can vary among different end organs (i.e., cochlea, utricle, saccule and cristae in mammals). Sajan et al. [41] found unique gene expression signatures for the mouse cochlea, utricle and saccule. This is relevant to hair cell regeneration research, because there is evidence for limited hair cell regeneration in the mammalian utricle [47,48,49], but not in the cochlea. Thus, differences in gene expression between the separate auditory end organs are not surprising. In contrast to the mammalian utricle, the avian utricle is in a constant process of apoptosis and regeneration [59,60,61,62]. The avian cochlea is similar to the mammalian cochlea, though, in that it is normally in a quiescent state [63]. Thus, comparing gene expression between different end organs may highlight potential therapeutic targets that may help guide mammalian cochlear sensory epithelia into a proliferative state, allowing for potential hair cell regeneration. Hawkins et al. [27] found 20 different inner ear genes and 80 transcription factors (TF) that were significantly different between the avian cochlea and utricle. Bmp4, Gata3, Gsn, Foxf1 and Prdm7 were some of the genes that were upregulated in the cochlea, while Smad2, Kit, β-amyloid, Loc51637, Hmg20b and Crip2 are examples of genes that were upregulated in the utricle. While some of these genes are well known to be involved in the development of the inner ear (e.g., Gata3 [64]), some of them were novel TF, like Loc51637 and Hmg20b, about which little was previously known.\nAt an even finer scale, the transcriptome of hair cells can be examined. Cristobal et al. [28] used laser capture microdissection to collect hair cells and supporting cells separately from the rat cristae to compare expression profiles between the two cell types. There were 97 and 78 annotated genes with greater than a five-fold expression difference in hair cells relative to supporting cells and supporting cells relative to hair cells, respectively [28]. Another means of separating hair cells from supporting cells for a pure hair cell transcriptome is to dissociate them from the sensory epithelia using proteases. McDermott et al. [43] isolated a population of pure hair cells from the zebrafish lagena and compared the hair cell transcriptome to that of control liver tissue. They found 1,037 hair cell-specific genes supporting a range of functions, including synaptic transmission, transcriptional control, membrane transport, cellular adhesion, cytoskeletal organization and signal transduction, as well as candidate deafness genes, such as KIDINS220.\n"}