Abstract
The adult mammalian cochlea lacks regenerative ability and the irreversible degeneration of cochlear sensory hair cells leads to permanent hearing loss. Previous data show that early postnatal cochlea harbors stem/progenitor-like cells and shows a limited regenerative/repair capacity. These properties are progressively lost later during the postnatal development. Little is known about the genes and pathways that are potentially involved in this difference of the regenerative/repair potentialities between early postnatal and adult mammalian cochlear sensory epithelia (CSE). The goal of our study is to investigate the transcriptomic profiles of these two stages. We used Mouse Genome 430 2.0 microarray to perform an extensive analysis of the genes expressed in mouse postnatal day-3 (P3) and adult CSE. Statistical analysis of microarray data was performed using SAM (Significance Analysis of Microarrays) software. We identified 5644 statistically significant differentially expressed transcripts with a fold change (FC) >2 and a False Discovery Rate (FDR) ≤0.05. The P3 CSE signature included 3,102 transcripts, among which were known genes in the cochlea, but also new transcripts such as, Hmga2 (high mobility group AT-hook 2) and Nrarp (Notch-regulated ankyrin repeat protein). The adult CSE overexpressed 2,542 transcripts including new transcripts, such as Prl (Prolactin) and Ar (Androgen receptor), that previously were not known to be expressed in the adult cochlea. Our comparative study revealed important genes and pathways differentially expressed between the developing and adult CSE. The identification of new candidate genes would be useful as potential markers of the maintenance or the loss of stem cells and regenerative/repair ability during mammalian cochlear development.
Highlights
Cochlear sensory epithelium (CSE) contains the auditory receptors refered to as hair cells (HCs) that are essential for hearing [1]
We showed that the supporting cells in the mouse postnatal cochlear sensory epithelia (CSE) express many stem/progenitor markers which were down regulated in the adult, that could be correlated to the loss of stem/progenitor cells within the adult mammalian cochlea [14]
In the postnatal day-3 (P3) cochlea, micro-dissected CSE samples included thickened areas formed by tall columnar cell mounds, i.e. the greater epithelial ridge (GER) and the lesser epithelial ridge (LER)
Summary
Cochlear sensory epithelium (CSE) contains the auditory receptors refered to as hair cells (HCs) that are essential for hearing [1]. HCs in mammals are produced only during embryonic development and not able to regenerate when lost during the postnatal period of maturation [2], some studies using in vitro assay suggested a limited non-proliferative regeneration/repair capacity within the ototoxic-damaged explants derived from the early postnatal CSE [3,4,5]. Recent studies demonstrated the presence of stem/progenitor cells within the postnatal-P3 mouse CSE and their mitotic capacity to form clonal spheres when maintained under appropriate in vitro conditions [11,12,13,14] This stem cell population is progressively exhausted during later postnatal development [12]. Comparison of expression profiles between P3 and adult mouse CSE is hypothesized to identify differentially regulated genes involved in stem/progenitor cell maintenance and the capacity of this sensory epithelium for regeneration/repair
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