Dataset Information

Cochlear Sox2⁺ Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.

ABSTRACT: In the mammalian cochlea, spiral ganglion neurons (SGNs) relay the acoustic information to the central auditory circuits. Degeneration of SGNs is a major cause of sensorineural hearing loss and severely affects the effectiveness of cochlear implant therapy. Cochlear glial cells are able to form spheres and differentiate into neurons in vitro. However, the identity of these progenitor cells is elusive, and it is unclear how to differentiate these cells toward functional SGNs. In this study, we found that Sox2⁺ subpopulation of cochlear glial cells preserves high potency of neuronal differentiation. Interestingly, Sox2 expression was downregulated during neuronal differentiation and Sox2 overexpression paradoxically inhibited neuronal differentiation. Our data suggest that Sox2⁺ glial cells are potent SGN progenitor cells, a phenotype independent of Sox2 expression. Furthermore, we identified a combination of small molecules that not only promoted neuronal differentiation of Sox2^- glial cells, but also removed glial cell identity and promoted the maturation of the induced neurons (iNs) toward SGN fate. In summary, we identified Sox2⁺ glial subpopulation with high neuronal potency and small molecules inducing neuronal differentiation toward SGNs.

SUBMITTER: Chen Z

PROVIDER: S-EPMC8490772 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Cochlear Sox2<sup>+</sup> Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.

Chen Zhen Z Huang Yuhang Y Yu Chaorong C Liu Qing Q Qiu Cui C Wan Guoqiang G

Frontiers in cell and developmental biology 20210921

In the mammalian cochlea, spiral ganglion neurons (SGNs) relay the acoustic information to the central auditory circuits. Degeneration of SGNs is a major cause of sensorineural hearing loss and severely affects the effectiveness of cochlear implant therapy. Cochlear glial cells are able to form spheres and differentiate into neurons <i>in vitro</i>. However, the identity of these progenitor cells is elusive, and it is unclear how to differentiate these cells toward functional SGNs. In this study ...[more]

PMID: 34621745

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Project description:The goals of this study were to derive a frequency-position function for the human cochlear spiral ganglion (SG) to correlate represented frequency along the organ of Corti (OC) to location along the SG, to determine the range of individual variability, and to calculate an "average" frequency map (based on the trajectories of the dendrites of the SG cells). For both OC and SG frequency maps, a potentially important limitation is that accurate estimates of cochlear place frequency based upon the Greenwood function require knowledge of the total OC or SG length, which cannot be determined in most temporal bone and imaging studies. Therefore, an additional goal of this study was to evaluate a simple metric, basal coil diameter that might be utilized to estimate OC and SG length. Cadaver cochleae (n = 9) were fixed <24 h postmortem, stained with osmium tetroxide, microdissected, decalcified briefly, embedded in epoxy resin, and examined in surface preparations. In digital images, the OC and SG were measured, and the radial nerve fiber trajectories were traced to define a series of frequency-matched coordinates along the two structures. Images of the cochlear turns were reconstructed and measurements of basal turn diameter were made and correlated with OC and SG measurements. The data obtained provide a mathematical function for relating represented frequency along the OC to that of the SG. Results showed that whereas the distance along the OC that corresponds to a critical bandwidth is assumed to be constant throughout the cochlea, estimated critical band distance in the SG varies significantly along the spiral. Additional findings suggest that measurements of basal coil diameter in preoperative images may allow prediction of OC/SG length and estimation of the insertion depth required to reach specific angles of rotation and frequencies. Results also indicate that OC and SG percentage length expressed as a function of rotation angle from the round window is fairly constant across subjects. The implications of these findings for the design and surgical insertion of cochlear implants are discussed.

Dataset Information

Cochlear Sox2⁺ Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.

Publications

Cochlear Sox2<sup>+</sup> Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.

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Dataset Information

Cochlear Sox2+ Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.

Publications

Cochlear Sox2<sup>+</sup> Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Cochlear Sox2⁺ Glial Cells Are Potent Progenitors for Spiral Ganglion Neuron Reprogramming Induced by Small Molecules.