Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

Frontiers in Cell and Developmental Biology
Teppei NodaAlain Dabdoub

Abstract

Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of bothAscl1andNeuroD1 in vitrogenerated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus n...Continue Reading

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Citations

Feb 7, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiang LiZhiyong Liu
Apr 5, 2020·Stem Cells·Judith S KempfleAlbert S B Edge
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Oct 6, 2020·Frontiers in Cell and Developmental Biology·Valentin Milichko, Vyacheslav Dyachuk
Oct 9, 2021·Frontiers in Cell and Developmental Biology·Zhen ChenGuoqiang Wan

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Datasets Mentioned

BETA
GSE107461

Methods Mentioned

BETA
cochlear implants
transfection
chip
Assay
RNA-Seq
PCR
fluorescence-activated cell sorting
PCA
RNAseq

Software Mentioned

TopHat2
QuantaSoft
HISAT2
FACSDiva

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