Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae

@article{Ono2009SilencingPR,
  title={Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae},
  author={Kazuya Ono and Takayuki Nakagawa and Ken Kojima and Masahiro Matsumoto and Takeshi Kawauchi and Mikio Hoshino and Juichi Ito},
  journal={Molecular and Cellular Neuroscience},
  year={2009},
  volume={42},
  pages={391-398}
}
The post-natal cochlear mammalian epithelium have no capacity to proliferate in tissue, however, dissociated supporting cells exhibit the ability to divide and trans-differentiate into new hair cells in vitro, with this process found to be correlated with the downregulation of the cyclin-dependent kinase inhibitor p27(kip1). Here we show that knockdown of p27(kip1) with short hairpin RNA-expressing vectors results in the cell-cycle reentry of post-mitotic supporting cells in the post-natal… Expand
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p27Kip1 is required to maintain proliferative quiescence in the adult cochlea and pituitary
TLDR
Re-establishment of normal p27Kip1 expression in animals with established pituitary tumors, in an inducible “knock-on” model, led to cessation ofpituitary tumor growth, indicating the cells had maintained their susceptibility to p27-mediated growth suppression. Expand
Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression
TLDR
Intensive barriers that limit proliferative capacity of utricular supporting cells are revealed that limit the ability of these cells to regenerate. Expand
The Cyclin Dependent Kinase Inhibitor p27 Kip1 Maintains Terminal Differentiation in the Mouse Organ of Corti
TLDR
It is reported that p27 deletion results in an increased number of inner and outer hair cells at one month of age and these hair cells display normal phenotypes including uptake of AM1-43, a mechanotransduction dye. Expand
p27Kip1 Knockdown Induces Proliferation in the Organ of Corti in Culture after Efficient shRNA Lentiviral Transduction
TLDR
The results revalidate the use of lentiviral vectors in the study and in the potential therapeutic approaches for inner ear diseases, as well as demonstrate that efficient manipulation of p27Kip1 is sufficient to induce significant proliferation in the postnatal cochlea. Expand
p27Kip1 down-regulation as achieved by two clinically feasible means did not induce proliferation of supporting cells in the rat neonatal cochlea in vivo
TLDR
It is proposed that the level of isolated modification of p27Kip1 expression in living mammals achievable through these approaches is insufficient to induce proliferation of supporting cells in the P0 neonatal rat cochlea in vivo. Expand
Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair Cells and Supporting Cells
TLDR
Unscheduled proliferation of SCs in the adult p130−/− cochlea coupled to downregulation of bona fide cell cycle inhibitors provides a mechanistic basis for the role of p130 as a regulator of SC and HC mitotic quiescence in the more apical regions of the cochrea. Expand
MYC Gene Delivery to Adult Mouse Utricles Stimulates Proliferation of Postmitotic Supporting Cells In Vitro
TLDR
The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore regenerative potential to supporting cells within the adult mammalian inner ear. Expand
Regulation of p27Kip1 by Sox2 Maintains Quiescence of Inner Pillar Cells in the Murine Auditory Sensory Epithelium
TLDR
The studies suggest that manipulating Sox2 or p27Kip1 expression is an effective approach to inducing proliferation of neonatal auditory IPCs, an initial but necessary step toward restoring hearing in mammals. Expand
Cell type-specific effects of p27KIP1 loss on retinal development
TLDR
Although expressed in all retinal cell types, p27 is required to maintain the quiescence of specific cell types including bipolar cells, Müller glia, and cones while it is dispensable for preventing cell cycle reentry in other cell types. Expand
LSD1 is Required for Hair Cell Regeneration in Zebrafish
TLDR
The data suggest that downregulation of LSD1 significantly decreases hair cell regeneration after neomycin-induced hair cell loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways, which might represent a novel biomarker and potential therapeutic approach for the treatment of hearing loss. Expand
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