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

Stem Cell Res Ther. 2019 Dec 2;10(1):365. doi: 10.1186/s13287-019-1437-0.

Abstract

Background: 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 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.

Methods: Here, 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.

Results: Consistent 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.

Conclusions: In 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.

Keywords: Differentiation; Gene expression; Proliferation; RNA-seq; Sphere formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cluster Analysis
  • Cochlea / cytology
  • Cochlea / metabolism*
  • Mice
  • Mice, Transgenic
  • Principal Component Analysis
  • Receptors, Notch / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome*
  • Transforming Growth Factor beta / metabolism
  • Wnt Signaling Pathway

Substances

  • Cell Cycle Proteins
  • Receptors, Notch
  • SOXB1 Transcription Factors
  • Transcription Factors
  • Transforming Growth Factor beta