Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals a Lmx1a Population in the Cochlea

Grandi, Fiorella C.; Tomasi, Lara De; Mustapha, Mirna

doi:10.3389/fnmol.2020.00083

Cited by 19 publications

(11 citation statements)

References 77 publications

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“…These Prph- eGFP-positive type II cell bodies are not uniformly located throughout the spiral ganglion. Instead, these Prph- eGFP-positive cell bodies appear to be more concentrated along the distal region of the spiral ganglion ( Figures 1C–F″ ), consistent with reports using antibody labeling ( Hafidi, 1998 ; Nayagam et al, 2011 ; Defourny et al, 2013 ; Grandi et al, 2020 ). This asymmetrical distribution was better visualized with NeuN labeling of Prph- eGFP mice to label all SGN nuclei ( Figure 2A ).…”

Section: Resultssupporting

confidence: 88%

“…As in this previous study with peripherin antibodies, once Prph-eGFP became restricted, specifically type II SGN cell bodies, they remained restricted throughout adulthood ( Figure 1 ), suggesting that Prph- eGFP is a useful marker for mature type II SGN perikarya. The unique localization to the distal region of the spiral ganglia ( Figure 2 ) has been reported ( Berglund and Ryugo, 1987 ; Hafidi, 1998 ; Nayagam et al, 2011 ; Maison et al, 2016 ; Grandi et al, 2020 ); however, we observed that this primarily distal distribution of type II SGNs was not uniform along the cochlea.…”

Section: Discussionsupporting

confidence: 40%

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Developmental Changes in Peripherin-eGFP Expression in Spiral Ganglion Neurons

Elliott

Kersigo

Lee

et al. 2021

Front. Cell. Neurosci.

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The two types of spiral ganglion neurons (SGNs), types I and II, innervate inner hair cells and outer hair cells, respectively, within the mammalian cochlea and send another process back to cochlear nuclei in the hindbrain. Studying these two neuronal types has been made easier with the identification of unique molecular markers. One of these markers, peripherin, was shown using antibodies to be present in all SGNs initially but becomes specific to type II SGNs during maturation. We used mice with fluorescently labeled peripherin (Prph-eGFP) to examine peripherin expression in SGNs during development and in aged mice. Using these mice, we confirm the initial expression of Prph-eGFP in both types I and II neurons and eventual restriction to only type II perikarya shortly after birth. However, while Prph-eGFP is uniquely expressed within type II cell bodies by P8, both types I and II peripheral and central processes continue to express Prph-eGFP for some time before becoming downregulated. Only at P30 was there selective type II Prph-eGFP expression in central but not peripheral processes. By 9 months, only the type II cell bodies and more distal central processes retain Prph-eGFP expression. Our results show that Prph-eGFP is a reliable marker for type II SGN cell bodies beyond P8; however, it is not generally a suitable marker for type II processes, except for central processes beyond P30. How the changes in Prph-eGFP expression relate to subsequent protein expression remains to be explored.

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Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 40%

Developmental Changes in Peripherin-eGFP Expression in Spiral Ganglion Neurons

Elliott

Kersigo

Lee

et al. 2021

Front. Cell. Neurosci.

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“…Expression in human type I spiral ganglion neurons is consistent with previous results in mice that used in situ hybridization and singlecell RNA analysis to demonstrate Lmx1a expression in a discrete type I spiral ganglion neuron subpopulation in the developing mouse cochlea [127]. These subtypes have been hypothesized to correspond to different excitation potentials thresholds [127] and enable further encoding of auditory information at the level of the spiral ganglion [128]. LMX1A encodes a transcription factor, LIM homeobox transcription factor 1-alpha, which is involved in neuronal differentiation as well as maintenance of neuronal homeostasis in the adult brain [129].…”

Section: Focal Adhesion Kinase 1 (Fak)supporting

confidence: 90%

A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens

Liu

Johansson

Rask‐Andersen

et al. 2021

BMC Med

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Background Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated. Methods We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4. Results All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss. Conclusions Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.

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“…Knockout of FZD2 in the mouse cochlea results in defects in OHC number and orientation, which are most severe in the apical region. In addition, a recent study identified FZD2 as a signature gene in one of three distinct SGN I populations by using single-cell transcriptome ( Grandi et al, 2020 ). In the mouse cochlea, planar polarity is guided by the PCP proteins FZD3 and FZD6.…”

Section: Roles Of Class F G Protein-coupled Receptors In Cochleamentioning

confidence: 99%

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

Guo²,

Fu³

et al. 2022

Front. Mol. Neurosci.

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The prevalence of hearing loss-related diseases caused by different factors is increasing worldwide year by year. Currently, however, the patient’s hearing loss has not been effectively improved. Therefore, there is an urgent need to adopt new treatment measures and treatment techniques to help improve the therapeutic effect of hearing loss. G protein-coupled receptors (GPCRs), as crucial cell surface receptors, can widely participate in different physiological and pathological processes, particularly play an essential role in many disease occurrences and be served as promising therapeutic targets. However, no specific drugs on the market have been found to target the GPCRs of the cochlea. Interestingly, many recent studies have demonstrated that GPCRs can participate in various pathogenic process related to hearing loss in the cochlea including heredity, noise, ototoxic drugs, cochlear structure, and so on. In this review, we comprehensively summarize the functions of 53 GPCRs known in the cochlea and their relationships with hearing loss, and highlight the recent advances of new techniques used in cochlear study including cryo-EM, AI, GPCR drug screening, gene therapy vectors, and CRISPR editing technology, as well as discuss in depth the future direction of novel GPCR-based drug development and gene therapy for cochlear hearing loss. Collectively, this review is to facilitate basic and (pre-) clinical research in this area, and provide beneficial help for emerging GPCR-based cochlear therapies.

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Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals a Lmx1a Population in the Cochlea

Cited by 19 publications

References 77 publications

Developmental Changes in Peripherin-eGFP Expression in Spiral Ganglion Neurons

Developmental Changes in Peripherin-eGFP Expression in Spiral Ganglion Neurons

A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

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