Intrinsic regenerative potential of murine cochlear supporting cells

Abstract

The lack of cochlear regenerative potential is the main cause for the permanence of hearing loss. Albeit quiescent in vivo, dissociated non-sensory cells from the neonatal cochlea proliferate and show ability to generate hair cell-like cells in vitro. Only a few non-sensory cell-derived colonies, however, give rise to hair cell-like cells, suggesting that sensory progenitor cells are a subpopulation of proliferating non-sensory cells. Here we purify from the neonatal mouse cochlea four different non-sensory cell populations by fluorescence-activated cell sorting (FACS). All four populations displayed proliferative potential, but only lesser epithelial ridge and supporting cells robustly gave rise to hair cell marker-positive cells. These results suggest that cochlear supporting cells and cells of the lesser epithelial ridge show robust potential to de-differentiate into prosensory cells that proliferate and undergo differentiation in similar fashion to native prosensory cells of the developing inner ear.

Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line

“…This lack of regenerative capacity is at odds with evidence that multipotent progenitor cells reside in the mammalian cochlea and can produce hair cells under appropriate conditions in vitro (1)(2)(3)(4). Unlike those cells of the mammalian ear, progenitor cells in nonmammalian vertebrates readily regenerate hair cells throughout life (5,6).…”

Sensory hair cell development and regeneration: similarities and differences

“…However, the quantity of colony-forming cells rapidly decreases from the neonatal to adult period (Oshima et al, 2007;White et al, 2006), implying a loss of stem cells and/or their accompanying niche. Several groups have used various defined markers to segregate distinct populations of cells in the neonatal cochlea (Chai et al, 2012;Jan et al, 2013;Oshima et al, 2007;Savary et al, 2007;Shi et al, 2012;Sinkkonen et al, 2011;White et al, 2006). Together, these studies suggest that Lgr5, which marks somatic stem cells in self-renewing organs (Barker et al, 2007;Jaks et al, 2008), is a promising enrichment marker for supporting cells that behave as hair cell progenitors in vitro.…”

Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway

“…Finally, frequent injections of EdU (twice a day) for 3 and 7 d in vivo or continuous presence of EdU in the culture media may increase the chance of identifying dividing cells. (10,14,45). However, these proliferative competent cells remain mitotic quiescent in the cochlear sensory epithelia of newborn mice in vivo.…”