4.7 Article

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

Journal

STEM CELL RESEARCH & THERAPY
Volume 10, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13287-019-1437-0

Keywords

RNA-seq; Proliferation; Differentiation; Sphere formation; Gene expression

Funding

  1. National Key R&D Program of China [2017YFA0103903]
  2. Chinese Academy of Science [XDA16010303]
  3. National Natural Science Foundation of China [81622013, 81970882, 81900941, 81570919, 81870721, 81771019, 81700913, 81670928, 81570921]
  4. Jiangsu Province Natural Science Foundation [BK20190121]
  5. Boehringer Ingelheim Pharma GmbH
  6. Fundamental Research Funds for the Central Universities [2242018k1G011]
  7. Open Research Fund of the State Key Laboratory of Genetic Engineering, Fudan University [SKLGE1809]
  8. Project of Invigorating Health Care through Science, Technology and Education

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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 Sox2(GFP/+) 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.

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