Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

Liu, Huizhan; Giffen, Kimberlee P.; Chen, Lei; Henderson, Heidi J; Cao, Talia A.; Kozeny, Grant A.; Beisel, Kirk W.; Li, Yi; He, David Z.Z.

doi:10.1016/j.celrep.2022.110665

Cited by 48 publications

(42 citation statements)

References 71 publications

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“…Miat probe (#432521) and the RNAscope ® 2.5 HD Detection Reagents-RED (#322360) were ordered from ACD. Manufacture’s instruction and Liu et al’s (2022) protocol were followed for the RNAscope. The following antibodies were used for immunostaining: Pcp4 (1:200, #HPA005792, Prestige Antibodies), goat anti-rabbit secondary antibody (1:800, #A-11011, Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics

Pass

et al. 2022

Front. Cell. Neurosci.

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Juvenile and mature mouse cochleae contain various low-abundant, vulnerable sensory epithelial cells embedded in the calcified temporal bone, making it challenging to profile the dynamic transcriptome changes of these cells during maturation at the single-cell level. Here we performed the 10x Genomics single-cell RNA sequencing (scRNA-seq) of mouse cochleae at postnatal days 14 (P14) and 28. We attained the transcriptomes of multiple cell types, including hair cells, supporting cells, spiral ganglia, stria fibrocytes, and immune cells. Our hair cell scRNA-seq datasets are consistent with published transcripts from bulk RNA-seq. We also mapped known deafness genes to corresponding cochlear cell types. Importantly, pseudotime trajectory analysis revealed that inner hair cell maturation peaks at P14 while outer hair cells continue development until P28. We further identified and confirmed a long non-coding RNA gene Miat to be expressed during maturation in cochlear hair cells and spiral ganglia neurons, and Pcp4 to be expressed during maturation in cochlear hair cells. Our transcriptomes of juvenile and mature mouse cochlear cells provide the sequel to those previously published at late embryonic and early postnatal ages and will be valuable resources to investigate cochlear maturation at the single-cell resolution.

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Section: Methodsmentioning

confidence: 99%

Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics

Pass

et al. 2022

Front. Cell. Neurosci.

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“…The DPOAE component at the frequency of 2f 1 -f 2 was measured in response to the two-tone bursts. The DPOAE threshold is defined as the f 1 sound pressure level (measured in decibels) required to produce a repeatable response above the noise level at the frequency of 2f 1 -f 2 ( 16 ).…”

Section: Methodsmentioning

confidence: 99%

Occlusion of two semicircular canals does not disrupt normal hearing in adult mice

Wang

Liu

et al. 2022

Front. Neurol.

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Vertigo is a debilitating disease affecting 15–20% of adults worldwide. Vestibular peripheral vertigo is the most common cause of vertigo, often due to Meniere's disease and benign paroxysmal positional vertigo. Although some vertigo symptoms can be controlled by conservative treatment and/or vestibular rehabilitation therapy, these treatments do not work for some patients. Semicircular canal occlusion surgery has proven to be very effective for these patients with intractable vertigo. However, its application is limited due to concern that the procedure will disrupt normal hearing. In this study, we investigated if occlusion of two semicircular canals would jeopardize auditory function by comparing auditory function and hair cell morphology between the surgical and contralateral ears before and after the surgery in a mouse model. By measuring the auditory brainstem response and distortion product otoacoustic emission 4 weeks post-surgery, we show that auditory function does not significantly change between the surgical and contralateral ears. In addition, confocal imaging has shown no hair cell loss in the cochlear and vestibular sensory epithelia, and scanning electron microscopy also indicates normal stereocilia morphology in the surgical ear. More importantly, the endocochlear potential measured from the surgical ear is not significantly different than that seen in the contralateral ear. Our study suggests that occlusion of two semicircular canals does not disrupt normal hearing in the mouse model, providing a basis to extend the procedure to patients, even those with normal hearing, benefitting more patients with intractable vertigo attacks.

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“…PMCA2w/a missense mutation causes deafness and balance disorders in humans (Bortolozzi and Mammano, 2018) Nox (NADPH oxidases) Expression in the cochlea and vestibule (Kiss et al, 2006;Xu et al, 2021) The main otolith components and factors necessary for calcium carbonate crystallization (Xu et al, 2021) The absence of NOX3 enhances hearing recovery after noise trauma (Rousset et al, 2022) CA (carbonic anhydrase) Expression in the cochlea and vestibule (Tohse and Mugiya, 2001;Matsumoto et al, 2017;Liu et al, 2022) Maintaining the right pH to promote otolith development and regulate otolith growth (Tohse et al, 2006;Matsumoto et al, 2017) CA inhibitors can cause hearing loss, and inhibit calcification of otoliths (Tohse and Mugiya, 2001;Liu et al, 2022) human hearing and vestibular disorders, and DFNA9, is secreted by small specialized areas of vestibular system epithelia whereby cells secrete Cochlin to the ear lumen and base of the basal lamina. Cochlin secreted from the base diffuses along the basal surface of vestibular epithelium, and is apically secreted and integrated into otolith.…”

Section: Pmca2mentioning

confidence: 99%

“…The CA inhibitor ethoxyzolamide inhibits the accumulation of bicarbonate in the endolymph and otolith, inhibits otolith calcification, and induces apoptosis of inner ear hair cells. Apoptosis of hair cells can lead to varying degrees of hearing loss ( Tohse and Mugiya, 2001 ; Liu et al, 2022 ).…”

Section: Important Factors Affecting the Formation And Maintenance Of...mentioning

confidence: 99%

Advances in otolith-related protein research

Huang

Qian

2022

Front. Neurosci.

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Otoliths are biological crystals formed by a layer of calcium carbonate crystal that adhere to the ciliary surface of the utricular and saccular receptors in the vestibule of all vertebrates inner ear, enabling the utricle and saccule to better perceive the changes in linear and gravitational acceleration. However, the molecular etiology of otolith related diseases is still unclear. In this review, we have summarized the recent findings and provided an overview of the proteins that play important roles in otolith formation and maintenance (Otoconin-90, Otolin-1, Otolith Matrix Protein-1, Cochlin, Otogelin, α-Tectorin, β-Tectorin, Otopetrin-1, and Otopetrin-2, PMCA2, etc.), providing new insight for the prevention and management of benign paroxysmal positional vertigo (BPPV) with basis for otolith-related proteins as potential biomarkers of vestibular disease.

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Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

Cited by 48 publications

References 71 publications

Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics

Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics

Occlusion of two semicircular canals does not disrupt normal hearing in adult mice

Advances in otolith-related protein research

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