Age-related transcriptome changes in Sox2+ supporting cells in the mouse cochlea

Cheng Cheng,Fangyi Chen,Waqas Muhammad,Mingliang Tang,Yunfeng Wang,Xiaoling Lu,Renjie Chai,Ling Lu,Junyan Gao,Xia Gao,Liyan Zhang,Weijie Zhu,Huawei Li,Luo Guo

doi:10.1186/s13287-019-1437-0

Abstract

BackgroundInner ear supporting cells (SCs) in the neonatal mouse cochlea are a potential source for hair cell (HC) regeneration, but several studies have shown that the regeneration ability of SCs decreases dramatically as mice age and that lost HCs cannot be regenerated in adult mice. To better understand how SCs might be better used to regenerate HCs, it is important to understand how the gene expression profile changes in SCs at different ages.MethodsHere, we used Sox2GFP/+ mice to isolate the Sox2+ SCs at postnatal day (P)3, P7, P14, and P30 via flow cytometry. Next, we used RNA-seq to determine the transcriptome expression profiles of P3, P7, P14, and P30 SCs. To further analyze the relationships between these age-related and differentially expressed genes in Sox2+ SCs, we performed gene ontology (GO) analysis.ResultsConsistent with previous reports, we also found that the proliferation and HC regeneration ability of isolated Sox2+ SCs significantly decreased as mice aged. We identified numerous genes that are enriched and differentially expressed in Sox2+ SCs at four different postnatal ages, including cell cycle genes, signaling pathway genes, and transcription factors that might be involved in regulating the proliferation and HC differentiation ability of SCs. We thus present a set of genes that might regulate the proliferation and HC regeneration ability of SCs, and these might serve as potential new therapeutic targets for HC regeneration.ConclusionsIn our research, we found several genes that might play an important role in regulating the proliferation and HC regeneration ability of SCs. These datasets are expected to serve as a resource to provide potential new therapeutic targets for regulating the ability of SCs to regenerate HCs in postnatal mammals.

Highlights

Hair cells (HCs) in the inner ear play a critical role in converting mechanical sound waves into neural signals for hearing and play a critical role in maintaining balance [1, 2]
We performed RNA-seq profiling of the Sox2+ Supporting cell (SC) isolated from Sox2GFP/+ transgenic mice at four different postnatal time points and determined the age-related differential expression of genes that might be involved in regulating the proliferation and HC differentiation ability of Sox2+ SCs
To further analyze the role of these age-related differentially expressed genes, we constructed a protein–protein interaction network using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). These datasets are expected to serve as a resource to provide potential new therapeutic targets for regulating the ability of SCs to regenerate HCs in postnatal mammals

Summary

Introduction

Hair cells (HCs) in the inner ear play a critical role in converting mechanical sound waves into neural signals for hearing and play a critical role in maintaining balance [1, 2]. In the mouse organ of Corti, HCs and supporting cells (SCs) emerge from the same inner ear prosensory cells. These inner ear prosensory cells start to exit the cell cycle from the apical turn to the basal turn of the cochlea. The inner ear prosensory cells start to differentiate into HCs and SCs beginning at the mid-base of the cochlea at around E13.5 and reaching the rest of the base and up to the apex of the cochlea over the few days [11]. Inner ear supporting cells (SCs) in the neonatal mouse cochlea are a potential source for hair cell (HC) regeneration, but several studies have shown that the regeneration ability of SCs decreases dramatically as mice age and that lost HCs cannot be regenerated in adult mice. To further analyze the relationships between these age-related and differentially expressed genes in Sox2+ SCs, we performed gene ontology (GO) analysis

Methods

Results

Conclusion