机构:[1]Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.[2]Augusta University/University of Georgia Medical Partnership, Athens, GA, USA.[3]Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.[4]Department of Otorhinolaryngology, Beijing Tongren Hospital, Beijing Capital Medical University, Beijing, China.临床科室耳鼻咽喉-头颈外科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[5]Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
Hair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian cochlear HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). To understand the genetic mechanisms underlying differences among adult zebrafish and mammalian cochlear HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. For example, both zebrafish and mouse HCs express Tmc1, Lhfpl5, Tmie, Cib2, Cacna1d, Cacnb2, Otof, Pclo and Slc17a8. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type. Tmc2 and Cib3 were not detected in adult mouse HCs but tmc2a and b and cib3 were highly expressed in zHCs. Mouse HCs express Kcna10, Kcnj13, Kcnj16, and Kcnq4, which were not detected in zHCs. Chrna9 and Chrna10 were expressed in mouse HCs. In contrast, chrna10 was not detected in zHCs. OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of slc26a5, and subsequently showed no voltage dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.
基金:
This work has been supported by NIH grant R01 DC004696 (to DH) from the NIDCD. The Imaging and Molecular Biology Cores at the Translational Hearing Research Center of Creighton University School of Medicine are supported by NIH grant 1P20GM139762 from the NIGMS, and by Béllucci Depaoli Family Foundation.
语种:
外文
PubmedID:
第一作者:
第一作者机构:[1]Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.[2]Augusta University/University of Georgia Medical Partnership, Athens, GA, USA.
通讯作者:
通讯机构:[1]Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.[2]Augusta University/University of Georgia Medical Partnership, Athens, GA, USA.
推荐引用方式(GB/T 7714):
Giffen Kimberlee P,Liu Huizhan,Yamane Kacey L,et al.Molecular Specializations Underlying Phenotypic Differences in Inner Ear Hair Cells of Zebrafish and Mice[J].Biorxiv : The Preprint Server For Biology.2024,doi:10.1101/2024.05.24.595729.
APA:
Giffen Kimberlee P,Liu Huizhan,Yamane Kacey L,Li Yi,Chen Lei...&He David Z Z.(2024).Molecular Specializations Underlying Phenotypic Differences in Inner Ear Hair Cells of Zebrafish and Mice.Biorxiv : The Preprint Server For Biology,,
MLA:
Giffen Kimberlee P,et al."Molecular Specializations Underlying Phenotypic Differences in Inner Ear Hair Cells of Zebrafish and Mice".Biorxiv : The Preprint Server For Biology .(2024)