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Direct reprogramming of spiral ganglion non-neuronal cells into neurons: Towards ameliorating sensorineural hearing loss by gene therapy

ABSTRACT: Direct reprogramming of spiral ganglion non-neuronal cells into neurons: Towards ameliorating sensorineural hearing loss by gene therapy

PROVIDER: PRJNA420108 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6327790_1.fastq.gz	Fastqsanger.gz
	SRR6327790_2.fastq.gz	Fastqsanger.gz
	SRR6327800_1.fastq.gz	Fastqsanger.gz
	SRR6327800_2.fastq.gz	Fastqsanger.gz
	SRR6327791_1.fastq.gz	Fastqsanger.gz

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Direct reprogramming of spiral ganglion non-neuronal cells into neurons: Towards ameliorating sensorineural hearing loss by gene therapy

Project description:The loss of primary auditory neurons (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 both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency and these iNs expressed several key markers of neuron identity. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, demonstrating that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.

2018-02-27 | GSE107461 | GEO

Transcriptomic analysis of the spiral ganglion from hearing and aminoglycoside deafened rats

Project description:We used RNAseq to assess transcriptomic changes in the spiral ganglion of rats deafened with kanamycin compared to hearing control rats to gain a better understanding of the deafening-induced changes that occur in the spiral ganglion. Transcriptomic profiles were obtained from whole spiral ganglion from hearing and deafened rats at P32 and P60. We observed significant changes in gene expression in not only deafened compared to hearing ganglia, but also from P32 to P60 in normal hearing animals. The most prominent change after deafening was an increase in immune response-related gene expression, indicating that immune response activation occurs in the deafened spiral ganglion.

2024-06-01 | GSE194063 | GEO

Microarray expression profiling of the spiral ganglion of hearing and deafened rats

Project description:Gene expression profiling of apical and basal halves of the spiral ganglion of hearing and kanamycin-deafened rats at P32 and P60 was performed using microarray analysis. The data are further described in Rahman MT, Bailey EM, Gansemer BM, Pieper AA, Manak JR, and Green SH. Anti-inflammatory compounds improve spiral ganglion neuron survival after aminoglycoside-induced hair cell loss in rats.

2023-04-26 | GSE190146 | GEO

Expression of Wnt Receptors in Adult Spiral Ganglion Neurons: Fzd 9 Located at Growth Cones of Regenerating Neurites

Project description:The fidelity of sound transmission by cochlear implants in patients with sensorineural hearing loss could be greatly improved by increasing the number of frequency channels. This could be achieved by stimulating and guiding neurite outgrowth to reduce the distance between the implant's electrodes and the remnants of the spiral ganglion neurons. However, little is known about signaling pathways, besides those of neurotrophic factors, that are operational in the adult spiral ganglion. To systematically identify neuronal receptors for guidance cues in the adult cochlea, we conducted a genome-wide cDNA microarray screen with two-month-old CBA/CaJ mice. A meta-analysis of our data and those from older mice in two other studies revealed the presence of neuronal transmembrane receptors that represent all four established guidance pathways—ephrin, netrin, semaphorin, and slit—in the mature cochlea as late as 15 months. In addition, we observed the expression of all known receptors for the Wnt morphogens, whose neuronal guidance function has only recently been recognized. In situ hybridizations located the mRNAs of the Wnt receptors frizzled 1, 4, 6, 9, and 10 specifically in adult spiral ganglion neurons. Finally, frizzled 9 protein was found in the growth cones of adult spiral ganglion neurons that were regenerating neurites in culture. We conclude from our results that adult spiral ganglion neurons are poised to respond to neurite damage, owing to the constitutive expression of a large and diverse collection of guidance receptors. Wnt signaling, in particular, emerges as a candidate pathway for guiding neurite outgrowth towards a cochlear implant after sensorineural hearing loss.

2009-09-16 | GSE12810 | GEO

Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly

2011-07-15 | GSE29766 | GEO

Transcriptomic analysis of the spiral ganglion from hearing and aminoglycoside deafened rats

Project description:Transcriptomic analysis of the spiral ganglion from hearing and aminoglycoside deafened rats

| PRJNA798973 | ENA

Microarray expression profiling of the spiral ganglion of hearing and deafened rats

Project description:Microarray expression profiling of the spiral ganglion of hearing and deafened rats

| PRJNA785989 | ENA

Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly

Project description:The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons at six developmental stages, ranging from embryonic day 12 (E12), when SG neurons first extend projections, up until postnatal day 15 (P15), after the onset of hearing. For comparison, we also analyzed the closely-related vestibular ganglion (VG) at the same time points. To identify genes involved in SG axon guidance and branching, target selection, synaptogenesis, synaptic refinement, and synaptic function, we collected SG at E12 and E13, E16, P0, P6, and P15. We also collected VG at the same time points. For E12 and E13 time points, SG and VG were microdissected from Rnx-cre; Z/EG embryos, which express GFP in the VG. E16-P15 VG was also isolated by microdissection from Rnx-cre; Z/EG animals. E16-P15 SG neurons were isolated by FACS sorting dissociated cochlea from Mafb-GFP animals.

2011-07-14 | E-GEOD-29766 | biostudies-arrayexpress

RNAseq of A/J mice spiral ganglion derived neurospheres vs differentiated auditory neurons

Project description:Sphere-forming progenitor cells can be isolated from the fetal and adult mammalian inner ear and give rise to inner ear specific cell types in vitro. Here, we provide phenotypical and functional characterization of a new pool of auditory progenitors as sustainable source for sphere-derived auditory neurons. The so-called phoenix auditory neuroprogenitors, isolated from the A/J mouse spiral ganglion, exhibit nearly unlimited intrinsic self-renewal properties (beyond 40 passages). At any passage, phoenix spheres can be efficiently differentiated by withdrawing growth factors into mature spiral ganglion cells, expressing both neurons and glial cells phenotypic markers and exhibiting similar functional properties as mouse spiral ganglion explants and human sphere-derived spiral ganglion cells. The present dataset includes RNAseq-based transcriptome analysis of phoenix auditory neurons following 7 days of differentiation. mRNA levels in differentiated cells are expressed relatively to neuroprogenitor spheres of equivalent passage (paired samples at passage 12, 21 and 36)

2020-08-29 | E-MTAB-9441 | biostudies-arrayexpress

Spiral ganglion subtype specification occurs prior to birth in the mouse

Project description:Little is known about the timing and factors which regulate the specification of neuronal subtypes in the cochlear spiral ganglion. Here we collect Spiral Ganglion Neurons (SGNs) from the mouse across four developmental timepoints (E14, E16, E18 and P1) in order to transciptionally profile their development.

2022-11-22 | GSE195500 | GEO

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