Transcript Profiling of Functionally Related Groups of Genes During Conditional Differentiation of a Mammalian Cochlear Hair Cell Line

Abstract

We have used Affymetrix high-density gene arrays to generate a temporal profile of gene expression during differentiation of UB/OC-1, a conditionally immortal cell line derived from the mouse cochlea. Gene expression was assessed daily for 14 days under differentiating conditions. The experiment was replicated in two separate populations of cells. Profiles for selected genes were correlated with those obtained by RT-PCR, TaqMan analysis, immunoblotting, and immunofluorescence. The results suggest that UB/OC-1 is derived from a population of nonsensory epithelial cells in the greater epithelial ridge that have the potential to differentiate into a hair-cell-like phenotype, without the intervention of Math1. Elements of the Notch signaling cascade were identified, including the receptorNotch3, with a transient up-regulation that suggests a role in hair cell differentiation. Several genes showed a profile similar toNotch3, including the transcriptional co-repressorGroucho1. UB/OC-1 also expressed Me1, a putative partner of Math1 that may confer competence to differentiate into hair cells. Cluster analysis revealed expression profiles for neural guidance genes associated with Gata3. The temporal dimension of this analysis provides a powerful tool to study genetic mechanisms that underlie the conversion of nonsensory epithelial cells into hair cells.

[The entire data set published in this paper has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus Database (http://www.ncbi.nlm.nih.gov/geo/) under the series accession no. GSE36 and sample numbers contained therein. Supplementary material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples or unpublished information as indicated in the paper: T. Hasson, C. Petit, and P. Matsudaira]