Transcript profiling of functionally related groups of genes during conditional differentiation of a mammalian cochlear hair cell line.
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 receptor Notch3, with a transient up-regulation that suggests a role in hair cell differentiation. Several genes showed a profile similar to Notch3, including the transcriptional co-repressor Groucho1. 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.
Rivolta
Marcelo N
MN
Institute of Molecular Physiology, Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom. m.n.rivolta@sheffield.ac.uk
Halsall
Antony
A
Johnson
Claire M
CM
Tones
Michael A
MA
Holley
Matthew C
MC
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D003053:Cochlear Duct / Q000166:cytology*; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005796:Genes / Q000235:genetics* / Q000502:physiology; D006198:Hair Cells, Auditory / Q000737:chemistry / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D011956:Receptors, Cell Surface / Q000235:genetics; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics; D013696:Temperature
D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch