Expression of candidate markers for stem/progenitor cells in the inner ears of developing and adult GFAP and nestin promoter-GFP transgenic mice.
Loss of hair cells in the mammalian cochlea leads to permanent sensori-neural hearing loss. Hair cells degenerate and their places are taken by phalangeal scars formed by non-sensory supporting cells. Current data indicate that early postnatal post-mitotic supporting cells can proliferate and differentiate into hair cell-like cells in culture. In this study, we used GFAP and nestin promoter-GFP transgenic mice in combination with other stem cell markers to characterize supporting cell subtypes in the postnatal day-3 (P3) and adult organs of Corti with potential stem/progenitor cell phenotype. In P3 organ of Corti, we show GFAP-GFP signal in all the supporting cell subtypes while the nestin-GFP was restricted to the supporting cells in the inner hair cell area. At this stage, GFAP and selected stem/progenitor markers displayed overlapping expression pattern in the supporting cell population. In the adult, GFAP expression is down-regulated from the supporting cells in the outer hair cell area and nestin expression is down-regulated in the supporting cells of the inner hair cell area. Sox2 and Jagged1 expression is maintained in the mature supporting cells, while Abcg2 was down-regulated in these cells. In contrast, GFAP and Abcg2 expression was up-regulated in the inner sulcus limbal cells outside the mature organ of Corti's area. Using quantitative reverse transcription-PCR, we found a decrease in transcripts for Jagged1 and Sox2 in adult cochleae. Our findings suggest that the loss of regenerative capacity of the adult organ of Corti is related to down-regulation of stem/progenitor key-markers from the mature supporting cells.
Smeti
Ibtihel
I
INSERM U583, Institute for Neurosciences of Montpellier, University of Montpellier I, 34091 Montpellier, France.
Savary
Etienne
E
Capelle
Vincent
V
Hugnot
Jean Philippe
JP
Uziel
Alain
A
Zine
Azel
A
D000818:Animals; D015415:Biomarkers; D003051:Cochlea / Q000166:cytology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006199:Hair Cells, Auditory, Inner / Q000166:cytology* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics; D064231:Nestin; D009925:Organ of Corti / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D049452:Green Fluorescent Proteins