Han-Gyu Bae, Sean Kashiwagura, Andrew Jung, Elizabeth Gould, Jun Hee Kim
{"title":"Haploinsufficiency of Whrn Contributes to Progressive Sensorineural Hearing Loss in C57BL6 Mice.","authors":"Han-Gyu Bae, Sean Kashiwagura, Andrew Jung, Elizabeth Gould, Jun Hee Kim","doi":"10.1007/s10162-025-00991-4","DOIUrl":"https://doi.org/10.1007/s10162-025-00991-4","url":null,"abstract":"<p><strong>Purpose: </strong>Whrn, encoding whirlin, is one of the genes highly relevant to Usher syndrome (USH) that has been known as an autosomal recessive genetic disorder that is characterized with sensorineural hearing loss with retinitis pigmentosa. Although recent studies on the other USH genes, PDZD7 and Ush1 g, showed a possibility of haploinsufficiency effect, the potential contribution of heterozygous Whrn loss to hearing loss remains unclear.</p><p><strong>Methods: </strong>To investigate the effect of Whrn haploinsufficiency, we conducted a longitudinal study assessing auditory function in heterozygous Whrn mutant (Whrn<sup>+/-</sup>) mice in which long isoform of Whrn was deleted by replacing exon 1 with Neo cassette without disturbing short isoform. The threshold of auditory brainstem responses (ABRs) was measured on 135 Whrn<sup>+/-</sup> mice and littermate 133 wild-type (WT) mice from 1 to 6 months of ages. From those data, the threshold from male and female were separately analyzed to investigate sex-dependent effect. To further investigate underlie mechanisms, hair cell death was investigated using immunohistostaining from 4 to 5 WT, 5 female Whrn<sup>+/-</sup>, and 7 male Whrn<sup>+/-</sup> mice at 4-5 months old.</p><p><strong>Results: </strong>Hearing threshold was significantly increased with aging in Whrn<sup>+/-</sup> mice compared to WT controls. Both WT and Whrn<sup>+/-</sup> mice exhibited sex-dependent variations in hearing sensitivity. Notably, Whrn<sup>+/-</sup> males showed a progressive hearing loss with age, while Whrn<sup>+/-</sup> females exhibited elevated hearing thresholds as early as 1-2 month of age compared to WT females.</p><p><strong>Conclusion: </strong>These results provide evidence for a haploinsufficiency effect of Whrn on auditory function and highlight its potential role in progressive sensorineural hearing loss.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher Bergevin, Dennis M Freeman, Allison Coffin
{"title":"How Exceptional Is the Ear?","authors":"Christopher Bergevin, Dennis M Freeman, Allison Coffin","doi":"10.1007/s10162-025-00988-z","DOIUrl":"https://doi.org/10.1007/s10162-025-00988-z","url":null,"abstract":"<p><p>Studies of hearing often conclude that the ear is \"remarkable\" or that its performance is \"exceptional.\" Some common examples include the following: <math><mo>▹</mo></math> the ears of mammals are encased in the hardest bone in the body; <math><mo>▹</mo></math> the ear contains the most vascularized tissue in body; <math><mo>▹</mo></math> the ear has the highest resting potential in the body; <math><mo>▹</mo></math> ears have a unique \"fingerprint\"; <math><mo>▹</mo></math> the ear can detect signals below the thermal noise floor; and <math><mo>▹</mo></math> the ear is highly nonlinear (or highly linear, depending upon who you ask). Some claims hold up to further scrutiny, while others do not. Additionally, several claims hold for animals in one taxon, while others are shared across taxa. Most frequently, our sense of wonder results from the differences between ears as products of natural selection (over eons) and artificial systems as products of engineering design. Our goal in analyzing claims of remarkable or exceptional performance is to deepen our appreciation of these differences.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arash Ebrahimian, Hossein Mohammadi, Hamid Motallebzadeh, Nima Maftoon
{"title":"Acoustical Effects of Tympanostomy Tube Attachment to Human Tympanic Membrane.","authors":"Arash Ebrahimian, Hossein Mohammadi, Hamid Motallebzadeh, Nima Maftoon","doi":"10.1007/s10162-025-00989-y","DOIUrl":"https://doi.org/10.1007/s10162-025-00989-y","url":null,"abstract":"<p><strong>Purpose: </strong>Several therapeutic approaches for hearing disorders involve attaching medical devices to the tympanic membrane. The attachment of these devices can change the mechanical and acoustical properties of the middle ear, affecting the middle-ear vibrations. The alteration of passive mechanical properties results from the mass, stiffness, and geometry of the attached device. Additionally, procedures like tympanostomy tube attachment create perforations on the tympanic membrane, altering both the mechanical and acoustical properties of the middle ear. This study examined the acoustical effects of these as well as the combination of acoustical and mechanical effects of the attached devices on middle-ear vibrations.</p><p><strong>Methods: </strong>A finite-element model of the middle ear, including the middle-ear cavity, was used to systematically study the effects of perforation size and location on vibration outputs. Experimental data from the literature were used to tune the model. This model was then employed to investigate the combined mechanical and acoustical effects of tympanostomy tubes on vibration outputs.</p><p><strong>Results: </strong>In presence of both the mechanical effects of the device (due to its mass and stiffness) and the acoustical effects of it (due to perforations), the reduction in the motion of the stapes footplate resulting from the acoustical effects is more remarkable at low frequencies (below about 1 kHz). However, at higher frequencies, the mechanical effects of the device are dominant.</p><p><strong>Conclusion: </strong>The findings of this study provide insights into the optimal design of the shape, location, and other characteristics of medical devices implanted on the tympanic membrane.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multidimensional Feature Analysis of Meniere's Disease and Vestibular Migraine: Insights from Machine Learning and Vestibular Testing.","authors":"Yi Du, Xingjian Liu, Lili Ren, Yu Wang, Ziming Wu","doi":"10.1007/s10162-025-00990-5","DOIUrl":"https://doi.org/10.1007/s10162-025-00990-5","url":null,"abstract":"<p><strong>Objective: </strong>Differentiating between Meniere's disease (MD) and vestibular migraine (VM) is challenging due to overlapping symptoms and limited diagnostic tools. Traditional statistical methods often rely on physician judgment and struggle with complex, high-dimensional data. This study applies the random forest (RF) machine learning algorithm to enhance the clinical differentiation between MD and VM.</p><p><strong>Methods: </strong>We retrospectively analyzed data from 36 VM (26 female) and 100 unilateral MD patients (51 female). The data were anonymized and labeled. Symptomatic and examination parameters were selected as features, and exploratory data analysis identified key parameters for diagnosis. An RF model was used to rank these features.</p><p><strong>Results: </strong>MD patients more commonly experienced ear-related symptoms, while VM patients reported more headaches and dizziness. Examination findings showed greater asymmetry in vHIT saccade latency in MD patients, particularly on the affected side. A total of 40 key parameters were identified. Heatmap and clustering analysis revealed that time constant (Tc) in velocity step test (VST) correlated more strongly with headache and other symptoms, while saccade latencies and velocities correlated with pure tone averages. The RF model selected 27 parameters for prediction, achieving 91.86% accuracy (95% confidence interval [85.37%, 95.18%]). Tc and saccade velocity were among the top 10 contributing features. Additionally, MD patients had earlier saccades and shorter Tc values on the affected side compared to both healthy controls and VM patients.</p><p><strong>Conclusions: </strong>Machine learning successfully classified MD and VM patients, with Tc and saccade velocity identified as key diagnostic indicators alongside symptoms.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M L A Fehrmann, L Haer-Wigman, H Kremer, H G Yntema, M E G Thijssen, E A M Mylanus, W J Huinck, C P Lanting, R J E Pennings
{"title":"Cochlear Implantation Outcomes in Genotyped Subjects with Sensorineural Hearing Loss.","authors":"M L A Fehrmann, L Haer-Wigman, H Kremer, H G Yntema, M E G Thijssen, E A M Mylanus, W J Huinck, C P Lanting, R J E Pennings","doi":"10.1007/s10162-025-00987-0","DOIUrl":"https://doi.org/10.1007/s10162-025-00987-0","url":null,"abstract":"<p><strong>Purpose: </strong>Cochlear implants (CIs) are an effective rehabilitation option for individuals with severe-to-profound sensorineural hearing loss (SNHL). While genetic factors play a significant role in SNHL, the variability in CI outcomes remains unclear. This study evaluated short- and long-term CI outcomes in a large genotyped cohort and investigated correlations with genetic defects and their cochlear site-of-lesion.</p><p><strong>Methods: </strong>This retrospective, single-center, cohort study included 220 subjects (127 females; 299 ears) with pathogenic variants identified in 31 different nuclear genes and in mitochondrial genes. Audiological outcomes were measured pre- and post-implantation. Cochlear site-of-lesion was categorized as pre-synaptic, post-synaptic, or mitochondrial, based on gene function or expression. Multiple regression analysis assessed factors influencing outcomes, including age at implantation, SNHL duration, hearing aid (HA) use, and cochlear site-of-lesion.</p><p><strong>Results: </strong>Results showed a median phoneme score of 90%, with better outcomes in early implantation (≤ 6 years). Variability in outcomes was not linked to cochlear site-of-lesion, but to subject-specific factors, such as age at implantation, duration of SNHL, pre-implantation HA use, and CI experience. A model incorporating these subject-specific factors explained 19% of the total variance in outcomes. Poorer outcomes (phoneme scores < 70%) were more common in individuals with prolonged auditory deprivation or older age at implantation.</p><p><strong>Conclusion: </strong>Genotyped CI recipients demonstrated excellent outcomes, with variability largely attributed to non-genetic factors. These findings show that cochlear implantation is a beneficial type of rehabilitation for most individuals with hereditary SNHL and underscore the importance of early implantation.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emmanuel Ponsot, Pauline Devolder, Ingeborg Dhooge, Sarah Verhulst
{"title":"Age-Related Decline in Neural Phase-Locking to Envelope and Temporal Fine Structure Revealed by Frequency Following Responses: A Potential Signature of Cochlear Synaptopathy Impairing Speech Intelligibility.","authors":"Emmanuel Ponsot, Pauline Devolder, Ingeborg Dhooge, Sarah Verhulst","doi":"10.1007/s10162-025-00985-2","DOIUrl":"https://doi.org/10.1007/s10162-025-00985-2","url":null,"abstract":"<p><strong>Purpose: </strong>Assessing the contribution of cochlear synaptopathy (CS) to the variability in speech-in-noise intelligibility among individuals remains a challenge. While several studies have proposed biomarkers for CS based on neural phase-locking to the temporal envelope (ENV), fewer have investigated how CS affects the coding of temporal fine structure (TFS), despite its crucial role in speech-in-noise perception. In this study, we specifically examined whether TFS-based markers of CS could be derived from electrophysiological responses and psychophysical detection thresholds of spectral modulation (SM) in a complex tone, which serves as a parametric model of speech.</p><p><strong>Methods: </strong>We employed an integrated approach, combining psychophysical testing with frequency-following response (FFR) measurements in three groups of participants: young normal-hearing (n = 15, 12 females, age 21 ± 1); older normal-hearing (n = 16, 11 females, age 47 ± 6); and older hearing-impaired (n = 14, 8 females, age 52 ± 6). We expanded on previous work by assessing phase-locking to both ENV, using a 4-kHz rectangular amplitude-modulated (RAM) tone, and TFS, using a low-frequency (< 1.5 kHz) SM complex tone.</p><p><strong>Results: </strong>Overall, FFR results showed significant reductions in neural phase-locking to both ENV and TFS components with age and hearing loss. Specifically, the strength of TFS-related FFRs, particularly the component corresponding to the harmonic closest to the peak of the spectral envelope (~ 500 Hz), was negatively correlated with age, even after adjusting for audiometric thresholds. This TFS marker also correlated with ENV-related FFRs derived from the RAM tone, suggesting a shared decline in phase-locking capacity across low and high cochlear frequencies. Computational simulations of the auditory periphery indicated that the observed FFR strength reduction with age is consistent with approximately 50% loss of auditory nerve fibers, aligning with histopathological data. However, the TFS-based FFR marker did not account for variability in speech intelligibility observed in the same participants. Psychophysical measurements showed no age-related effects and were unrelated to the TFS-based FFR marker, highlighting the need for further psychophysical research to establish a behavioral counterpart.</p><p><strong>Conclusion: </strong>Altogether, our results demonstrate that FFRs to vowel-like stimuli can serve as a complementary electrophysiological marker for assessing neural coding fidelity to stimulus TFS. This approach could provide a valuable tool for better understanding the impact of CS on an important coding dimension for speech-in-noise perception.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryohei Oya, Kwang Min Woo, Brian Fabella, R G Alonso, Paloma Bravo, A J Hudspeth
{"title":"Influence of Myosin Regulatory Light Chain and Myosin Light Chain Kinase on the Physiological Function of Inner Ear Hair Cells.","authors":"Ryohei Oya, Kwang Min Woo, Brian Fabella, R G Alonso, Paloma Bravo, A J Hudspeth","doi":"10.1007/s10162-025-00986-1","DOIUrl":"https://doi.org/10.1007/s10162-025-00986-1","url":null,"abstract":"<p><strong>Purpose: </strong>In the receptor organs of the inner ear, hair cells detect mechanical stimuli such as sounds and accelerations by deflection of their hair bundles. Myosin regulatory light chain (RLC) and non-muscle myosin II (NM2) are expressed at the apical surfaces of hair cells, and NM2 and the phosphorylation of RLC by myosin light chain kinase (MLCK) have earlier been shown to regulate the shapes of hair cells' apical surfaces in rodents. The aim of our study was to elucidate the function of myosin molecules on hair cell physiology.</p><p><strong>Methods: </strong>We investigated the expression of NM2 and RLC in the bullfrog's saccule by immunostaining. Using NM2 and MLCK inhibitors, we measured the stiffness, spontaneous oscillation, and resting open probability of frog hair bundles. Six to ten saccules from pleural animals were used in each experiment. In addition, we recorded auditory brainstem responses in ten mice after transtympanic injection of an MLCK inhibitor.</p><p><strong>Results: </strong>We confirmed the expression of NM2A/B and MYL9 on the apical surfaces of hair cells and of NM2A and MYL12A in hair bundles. We found that NM2 and MLCK inhibitors reduce the stiffness of hair bundles from the bullfrog's saccule. Moreover, MLCK inhibition inhibits the spontaneous oscillation of hair bundles and increases the resting open probability of transduction channels. In addition, MLCK inhibition elevates hearing thresholds in mice.</p><p><strong>Conclusion: </strong>We conclude that NM2 and the phosphorylation of RLC modulate the physiological function of hair cells and thereby help to set the normal operating conditions of hair bundles.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kara C Schvartz-Leyzac, Carolyn M McClaskey, James W Dias, Bryan E Pfingst, Kelly C Harris
{"title":"Contributions of Auditory Nerve Density and Synchrony to Speech Understanding in Older Cochlear Implant Users.","authors":"Kara C Schvartz-Leyzac, Carolyn M McClaskey, James W Dias, Bryan E Pfingst, Kelly C Harris","doi":"10.1007/s10162-025-00984-3","DOIUrl":"https://doi.org/10.1007/s10162-025-00984-3","url":null,"abstract":"<p><strong>Purpose: </strong>The majority of adult cochlear implant (CI) recipients are over the age of 65, and previous research in non-implanted older adults shows that auditory nerve (AN) pathophysiology contributes to senescent declines in speech understanding. However, age-related changes to AN structure and function have not yet been explored as a contributory factor to poorer speech understanding outcomes in older CI users. Here, we explore how estimates of AN disengagement (i.e., AN density) and dyssynchrony in CI users contribute to poorer speech recognition performance observed in older CI users.</p><p><strong>Methods: </strong>We examined electrically evoked compound action potentials (ECAPs) in 47 adult (Male = 25) CI recipients. We measured the interphase gap (IPG) effect for the amplitude-growth function (AGF) slope and the N1-P2 interpeak latency as independent metrics of AN density and dyssynchrony, respectively.</p><p><strong>Results: </strong>Estimates of AN density and dyssynchrony worsen with increasing age in older CI listeners. These measures were not significantly correlated with one another, but were independently related to speech recognition in noise performance. Lower ECAP IPG effect values (lower density of AN fibers) are observed in older CI users. Longer N1-P2 interpeak latency values (poorer neural synchrony) are also observed in older CI users. When controlling for listener age, poorer AN dyssynchrony contributes to declines in speech-recognition-in-noise performance in CI users.</p><p><strong>Conclusion: </strong>These results suggest that AN dyssynchrony rather than density is the primary contributing factor to age-related declines in speech understanding in CI users. These results have important implications for better understanding neural contributions to speech understanding in adult CI users.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David J Perkel, Christopher K Giardina, Joshua H Goldwyn, Julie G Arenberg
{"title":"Model-Based Inference of Electrode Distance and Neuronal Density from Measured Detection Thresholds in Cochlear Implant Listeners.","authors":"David J Perkel, Christopher K Giardina, Joshua H Goldwyn, Julie G Arenberg","doi":"10.1007/s10162-025-00978-1","DOIUrl":"10.1007/s10162-025-00978-1","url":null,"abstract":"<p><strong>Purpose: </strong>Cochlear implants (CI) are a highly successful neural prosthesis that can restore hearing in individuals with sensorineural hearing loss. However, the extent of hearing restoration varies widely. Two major factors likely contribute to poor performance: (1) the distances between electrodes and surviving spiral ganglion neurons and (2) the density of those neurons. Reprogramming the CI at a poor electrode-neuron interface, using focused tripolar stimulation or remapping the electrodes, would benefit from understanding the cause of the poor interface.</p><p><strong>Methods: </strong>We used a cochlear model with simplified geometry and neuronal composition to investigate how the interface affects stimulation thresholds. We then inverted the model to infer electrode distance and neuronal density from monopolar and tripolar threshold values obtained behaviorally. We validated this inverted model for known scenarios of electrode distance and neuronal density. Finally, we assessed the model using data from 18 CI users whose electrode distances were measured from CT imaging.</p><p><strong>Results: </strong>The inverted model accurately inferred electrode distance and neuronal density for known scenarios. It also reliably reproduced behavioral monopolar and tripolar threshold profiles for CI users, with mean prediction errors within 1 dB for 17/18 subjects. Fits of electrode distance were more variable; accuracy depended on the assumed value of temporal bone resistivity. Twelve subjects had minimum distance error (0.31 mm) using low resistivity (70 Ω-cm) while the others had better fits (0.30 mm) with higher resistivity (250 Ω-cm).</p><p><strong>Conclusion: </strong>This inverted model shows promise as a simple, practical tool to better assess and understand the electrode-neuron interface.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"185-201"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abel P David, Sushobhan Biswas, Macey P Soltis, Yasmin Eltawil, Ruiqi Zhou, Sarah A Easow, Alan G Cheng, Stefan Heller, Taha A Jan
{"title":"Crosstalk Signaling Between the Epithelial and Non-Epithelial Compartments of the Mouse Inner Ear.","authors":"Abel P David, Sushobhan Biswas, Macey P Soltis, Yasmin Eltawil, Ruiqi Zhou, Sarah A Easow, Alan G Cheng, Stefan Heller, Taha A Jan","doi":"10.1007/s10162-025-00980-7","DOIUrl":"10.1007/s10162-025-00980-7","url":null,"abstract":"<p><strong>Purpose: </strong>The otolith organs of the inner ear consist of the utricle and saccule that detect linear acceleration. These organs rely on mechanosensitive hair cells for transduction of signals to the central nervous system. In the murine utricle, about half of the hair cells are born during the first postnatal week. Here, we wanted to explore the role and interaction of the non-epithelial mesenchymal cells with the sensory epithelium and provide a resource for the auditory neurosciences community.</p><p><strong>Methods: </strong>We utilized full-length Smart-seq2 single-cell RNA sequencing at postnatal days 4 and 6 along with a host of computational methods to infer interactions between the epithelial and non-epithelial compartments of the mouse utricle. We validated these findings using a combination of immunohistochemistry and quantitative multiplex in situ hybridization.</p><p><strong>Results: </strong>We report diverse cell-cell crosstalk among the 12 annotated cell populations (n = 955 cells) in the developing neonatal mouse utricle, including epithelial and non-epithelial cellular signaling. The mesenchymal cells are the dominant signal senders during the postnatal period. Epithelial to mesenchymal signaling, as well as mesenchymal to epithelial signaling, are quantitatively shown through the TGFβ and pleiotrophin pathways.</p><p><strong>Conclusion: </strong>This study highlights the dynamic process of postnatal vestibular organ development that relies not only on epithelial cells, but also on crosstalk between spatial compartments and among different cell groups. We further provide a data-rich resource for the inner ear community.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"127-145"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}