Age-related transcriptome changes in Sox2+supporting cells in the mouse cochlea
Age-related transcriptome changes in Sox2+supporting cells in the mouse cochlea
复制标题
小鼠耳蜗 Sox2 支持细胞中与年龄相关的转录组变化。
DOI：
10.1186/s13287-019-1437-0
复制
发表时间：
2019-12-02
影响因子：
7.5
通讯作者：
Chai, Renjie
中科院分区：
文献类型：
--
作者：
Cheng, Cheng;Wang, Yunfeng;Chai, Renjie
背景新生小鼠耳蜗中的内耳支持细胞（SC）是毛细胞（HC）再生的潜在来源，但多项研究表明，SC的再生能力随着小鼠年龄的增长而急剧下降，并且成年小鼠中失去的HC无法再生。为了更好地了解SC如何更好地用于再生HC，重要的是要了解不同年龄的SC中基因表达谱如何变化。方法采用流式细胞术分离Sox 2（GFP/+）小鼠出生后第3、7、14、30天的Sox 2 + SC。接下来，我们使用RNA-seq来确定P3，P7，P14和P30 SC的转录组表达谱。为了进一步分析Sox 2 + SC中这些年龄相关和差异表达基因之间的关系，我们进行了基因本体论（GO）分析。结果与以往报道一致，分离的Sox 2 + SC增殖能力和HC再生能力随着年龄的增长而明显下降。我们确定了许多基因，富集和差异表达的Sox 2 + SC在四个不同的出生后年龄，包括细胞周期基因，信号通路基因，转录因子，可能参与调节的SC的增殖和HC分化能力。因此，我们提出了一组基因，可能会调节干细胞的增殖和HC再生能力，这些可能作为潜在的新的治疗目标HC再生。结论本研究中发现了几个可能在调控SC增殖和HC再生能力中起重要作用的基因。这些数据集有望作为一种资源，提供潜在的新的治疗靶点，用于调节SC在出生后哺乳动物中再生HC的能力。
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.