Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regenera...Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.展开更多
Hearing loss and deafness,as a worldwide disability disease,have been troubling human beings.However,the auditory organ of the inner ear is highly heterogeneous and has a very limited number of cells,which are largely...Hearing loss and deafness,as a worldwide disability disease,have been troubling human beings.However,the auditory organ of the inner ear is highly heterogeneous and has a very limited number of cells,which are largely uncharacterized in depth.Recently,with the development and utilization of single-cell RNA sequencing(scRNA-seq),researchers have been able to unveil the complex and sophisticated biological mechanisms of various types of cells in the auditory organ at the single-cell level and address the challenges of cellular heterogeneity that are not resolved through by conventional bulk RNA sequencing(bulk RNAseq).Herein,we reviewed the application of scRNA-seq technology in auditory research,with the aim of providing a reference for the development of auditory organs,the pathogenesis of hearing loss,and regenerative therapy.Prospects about spatial transcriptomic scRNA-seq,single-cell based genome,and Live-seq technology will also be discussed.展开更多
基金supported by the National Natural Science Foundation of China,No.81420108010,81271084,81200740,81371093
文摘Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.
基金supported by grants from National Key R&D Program of China(2021YFA1101300,2021YFA1101800,2020YFA0112503)Strategic Priority Research Program of the Chinese Academy of Science(XDA16010303)+3 种基金National Natural Science Foundation of China(82030029,81970882,and 92149304)Science and Technology Department of Sichuan Province(2021YFS0371)Shenzhen Fundamental Research Program(JCYJ20190814093401920,JCYJ20210324125608022)Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University(SKLGE-2104).
文摘Hearing loss and deafness,as a worldwide disability disease,have been troubling human beings.However,the auditory organ of the inner ear is highly heterogeneous and has a very limited number of cells,which are largely uncharacterized in depth.Recently,with the development and utilization of single-cell RNA sequencing(scRNA-seq),researchers have been able to unveil the complex and sophisticated biological mechanisms of various types of cells in the auditory organ at the single-cell level and address the challenges of cellular heterogeneity that are not resolved through by conventional bulk RNA sequencing(bulk RNAseq).Herein,we reviewed the application of scRNA-seq technology in auditory research,with the aim of providing a reference for the development of auditory organs,the pathogenesis of hearing loss,and regenerative therapy.Prospects about spatial transcriptomic scRNA-seq,single-cell based genome,and Live-seq technology will also be discussed.
