Journal ArticleDOI
Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells
Patricia M. White,Angelika Doetzlhofer,Yun Shain Lee,Andrew K. Groves,Andrew K. Groves,Neil Segil,Neil Segil +6 more
TLDR
It is shown that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture, and that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the able to downregulate the cyclin-dependent kinase inhibitor p27Kip1.Abstract:
Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.read more
Citations
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Journal ArticleDOI
The Histone H3 Lysine-27 Demethylase Jmjd3 Links Inflammation to Inhibition of Polycomb-Mediated Gene Silencing
Francesca De Santa,Maria Grazia Totaro,Elena Prosperini,Samuele Notarbartolo,Giuseppe Testa,Gioacchino Natoli +5 more
TL;DR: The discovery of an inducible enzyme that erases a histone mark controlling differentiation and cell identity provides a link between inflammation and reprogramming of the epigenome, which could be the basis for macrophage plasticity and might explain the differentiation abnormalities in chronic inflammation.
Journal ArticleDOI
Neuroepithelial Cells Supply an Initial Transient Wave of MSC Differentiation
Yasuhiro Takashima,Takumi Era,Kazuki Nakao,Saki Kondo,Masato Kasuga,Austin Smith,Shin-Ichi Nishikawa +6 more
TL;DR: It is shown that the earliest wave of MSC in the embryonic trunk is generated from Sox1+ neuroepithelium but not from mesoderm, concluding that MSC can be defined as a definite in vivo entity recruited from multiple developmental origins.
Journal ArticleDOI
Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma
Kunio Mizutari,Masato Fujioka,Masato Fujioka,Masato Fujioka,Makoto Hosoya,Naomi Bramhall,Naomi Bramhall,Hirotaka James Okano,Hideyuki Okano,Albert S.B. Edge,Albert S.B. Edge +10 more
TL;DR: It is shown that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro.
Journal ArticleDOI
Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear
Kazuo Oshima,Kazuo Oshima,Christian Grimm,C. Eduardo Corrales,C. Eduardo Corrales,Pascal Senn,Rodrigo Martinez Monedero,Gwenaëlle S. G. Géléoc,Albert S.B. Edge,Jeffrey R. Holt,Stefan Heller,Stefan Heller +11 more
TL;DR: These findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.
Journal ArticleDOI
Regulation of cell fate in the sensory epithelia of the inner ear.
TL;DR: The sensory epithelia of the inner ear contain mechanosensory hair cells and non-sensory supporting cells and new methodologies have resulted in significant steps forward in the understanding of the molecular pathways that direct cells towards these cell fates.
References
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Journal ArticleDOI
Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
Journal ArticleDOI
A Syndrome of Multiorgan Hyperplasia with Features of Gigantism, Tumorigenesis, and Female Sterility in p27Kip1-Deficient Mice
Matthew L. Fero,Michael J. Rivkin,Michael Tasch,Peggy L. Porter,Catherine E. Carow,Eduardo Firpo,Kornelia Polyak,Li-Huei Tsai,Virginia C. Broudy,Roger M. Perlmutter,Kenneth Kaushansky,James M. Roberts +11 more
TL;DR: P27 deficiency may cause a cell-autonomous defect resulting in enhanced proliferation in response to mitogens, and in the spleen, the absence of p27 selectively enhanced proliferation of hematopoietic progenitor cells.
Journal ArticleDOI
Math1: an essential gene for the generation of inner ear hair cells.
Nessan A. Bermingham,Bassem A. Hassan,Steven D. Price,Melissa A. Vollrath,Nissim Ben-Arie,Ruth Anne Eatock,Hugo J. Bellen,Anna Lysakowski,Huda Y. Zoghbi +8 more
TL;DR: Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia, and this gene is thus required for the genesis of hair cells.
Journal ArticleDOI
Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.
TL;DR: It is demonstrated that Fgfr3 is essential for normal endochondral ossification and inner ear development and Contrasts between the skeletal phenotype and achondroplasia suggest that activation of FGFR3 causes achondaplasia.
Journal ArticleDOI
Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears.
J L Zheng,Wei-Qiang Gao +1 more
TL;DR: It is reported here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells, and immature postnatal mammalian inner ears retained the competence to generate new hair cells.
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