About this Research Topic
The inner ear is responsible for our ability to hear and balance. Housed within the inner ear, the cochlea contains sensory hair cells (HCs) and spiral ganglion neurons (SGNs) that convert sound into neural signals. Exposure to loud sounds and ototoxic drugs causes loss of these cell types and leads to sensorineural hearing loss. In the U.S. alone, over 13% of the U.S. population (30 million people) has some form of diagnosed hearing loss. The number of people who suffer from hearing loss is likely higher as better diagnostic tools reveal symptoms of “hidden” hearing loss not observed in conventional audiograms. One major goal in the auditory field is to regenerate and replace loss HCs and SGNs to regain auditory function.
Using development as a roadmap, the strategy for repurposing transcription factors to alter transcriptional regulatory networks, change cellular transcriptomes and promote differentiation has been employed for regeneration. Study of the developing inner ear has posed many different challenges due to the small size of the organ and limited number of cells. Use of conventional and emerging single cell analysis methods provides a means to obtain insight into proliferation, specification and differentiation of HCs and SGNs.
Mouse inner ear development starts ~ E8.5 when ectoderm between rhombomeres 5 and 6 thickens to form the otic placode. As the otic placode invaginates to form the otic cup, cells from anteroventral region form the neurosensory domain are further specified to become the future HCs and SGNs. The neurosensory progenitor pool expresses different sets of transcription factors (TF) to determine cell fate, promote differentiation and maturation into multiple cell lineages. The function of transcriptional regulatory networks is modified by the epigenetic landscape of a cell. Chromatin remodeling proteins and microRNAs help determine the epigenetic status and contribute to proper development of HCs and SGNs. Each genetic and epigenetic factor alters the transcriptome to guide HC and SGN development. Using single cell transcriptome analysis, the dynamic changes that occur as these cells develop are being revealed. Genetically modified mice that mark otic cell types undergoing development allow harvesting single cells for deep sequencing. The heterogeneity of harvested cells allows pseudotemporal ordering transcriptomes and depicts the dynamically changing transcriptional landscape that reflects otic development. Repurposing these factors will help guide the transcriptome in pluripotent stem cells into otic cell types and accelerate efforts for inner ear stem cell therapies. The Research Topic will focus on the effects of genetic and epigenetic factors that affect otic neurosensory development and regeneration with an emphasis on single cell analysis techniques.
Keywords: chromatin, transcriptome, development, inner ear, cochlea, stem cell, regeneration
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