Pluripotent stem cells from the adult mouse inner ear

Li, Huawei; Liu, Hong; Heller, Stefan

doi:10.1038/nm925

Cited by 427 publications

(380 citation statements)

References 39 publications

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“…Additionally, it is well known that the subventricular zone in the mammalian brain is a stem cell niche that give rise to neurons, as well as to glial cells, and that these multipotent stem cells even persist in the adult brain [45,46]. Although the presence of stem cells in the zebrafish ear has not been studied yet, a study conducted on adult mice demonstrated that cells from the inner ear can be considered as stem cells, since they are able to self-renew and to differentiate in a variety of cell types, including the hair cells responsible for the transmission of the hearing stimuli [47]. As drCol 15a1b is expressed in those locations where neural stem cells reside, it can be used as a novel stem cell marker for neural stem cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of drCol 15a1b: A Novel Component of the Stem Cell Niche in the Zebrafish Retina

2010

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There is a clear need to develop novel tools to help improve our understanding of stem cell biology, and potentially also the utility of stem cells in regenerative medicine. We report the cloning, functional, and bioinformatic characterization of a novel stem cell marker in the zebrafish retina, drCol 15a1b. The expression pattern of drCol 15a1b is restricted to stem cell niches located in the central nervous system, whereas other collagen XVs are associated with muscle and endothelial tissues. Knocking down drCol 15a1b expression causes smaller eyes, ear defects, and brain edema. Microscopic analysis reveals enhanced proliferation in the morphant eye, with many mitotic nuclei located in the central retina, together with a delayed differentiation of the mature retinal cell types. Besides, several markers known to be expressed in the ciliary marginal zone display broader expression areas in morpholino-injected embryos, suggesting an anomalous diffusion of signaling effectors from the sonic hedgehog and notch pathways. These results indicate that drCol 15a1b is a novel stem cell marker in the central nervous system that has a key role in homing stem cells into specialized niches in the adult organism. Moreover, mutations in the hCol 18a1 gene are responsible for the Knobloch syndrome, which affects brain and retinal structures, suggesting that drCol 15a1b may function similarly to mammalian Col 18a1. Thus, our results shed new light on the signaling pathways that underlie the maintenance of stem cells in the adult organism while helping us to understand the role of extracellular matrix proteins in modulating the signals that determine stem cell differentiation, cell cycle exit and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Characterization of drCol 15a1b: A Novel Component of the Stem Cell Niche in the Zebrafish Retina

2010

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“…It has been suggested that new hair cells could be formed by regeneration (e.g., Li et al, 2003) or phenotypic trans-differentiation (e.g., Gao, 2003;Izumikawa et al, 2005) within the adult mammalian inner ear. The regenerative potential of adult SGNs, however, remains to be tested.…”

Section: Introductionmentioning

confidence: 99%

Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro

Wei

Jin

Järlebark

et al. 2006

Developmental Neurobiology

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ABSTRACT:The inner ear spiral ganglion is populated by bipolar neurons connecting the peripheral sensory receptors, the hair cells, with central neurons in auditory brain stem nuclei. Hearing impairment is often a consequence of hair cell death, e.g., from acoustic trauma. When deprived of their peripheral targets, the spiral ganglion neurons (SGNs) progressively degenerate. For effective clinical treatment using cochlear prostheses, it is essential to maintain the SGN population. To investigate their survival dependence, synaptogenesis, and regenerative capacity, adult mouse SGNs were separated from hair cells and studied in vitro in the presence of various neurotrophins and growth factors. Coadministration of fibroblast growth factor 2 (FGF-2) and glial cell line-derived neurotrophic factor (GDNF) provided support for long-term survival, while FGF-2 alone could strongly promote neurite regeneration.Fibroblast growth factor receptor FGFR-3-IIIc was found to upregulate and translocate to the nucleus in surviving SGNs. Surviving SGNs formed contacts with other SGNs after they were deprived of the signals from the hair cells. In coculture experiments, neurites extending from SGNs projected toward hair cells. Interestingly, adult mouse spiral ganglion cells could carry out both symmetric and asymmetric cell division and give rise to new neurons. The authors propose that a combination of FGF-2 and GDNF could be an efficient route for clinical intervention of secondary degeneration of SGNs. The authors also demonstrate that the adult mammalian inner ear retains progenitor cells, which could commit neurogenesis. '

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“…5 Recently, the cells with high proliferative index and pluripotency has been characterized in mouse vestibular sensory epithelia. 6 Moreover, the progenitor population of hair cells has been derived from the cochlea of neonatal rats. 7 Despite of the well-characterized pluripotency and stem cell-like property of supporting cells, stimulation of its trans-differentiating potential via medical approach for the therapeutic purpose is still challenging.…”

Section: Introductionmentioning

confidence: 99%

Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells

Han

Cong

et al. 2018

Organogenesis

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We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.

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Pluripotent stem cells from the adult mouse inner ear

Cited by 427 publications

References 39 publications

Characterization of drCol 15a1b: A Novel Component of the Stem Cell Niche in the Zebrafish Retina

Characterization of drCol 15a1b: A Novel Component of the Stem Cell Niche in the Zebrafish Retina

Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro

Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells

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