Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea.
Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea.
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小鼠耳蜗顶转和基转中 Lgr5 祖细胞转录组的表征。
DOI：
10.18632/oncotarget.8636
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发表时间：
2016-07-05
期刊：
影响因子：
--
通讯作者：
Chai R
中科院分区：
文献类型：
--
作者：
Waqas M;Guo L;Zhang S;Chen Y;Zhang X;Wang L;Tang M;Shi H;Bird PI;Li H;Chai R
Lgr 5+支持细胞（SC）是耳蜗中富集的毛细胞（HC）祖细胞，并且一些研究已经显示顶圈和底圈之间SC的增殖和HC再生能力的差异。然而，尚未研究顶端和基底Lgr 5 + SC的转录组之间的详细差异。我们发现，当通过FACS分离时，与来自基部的那些相比，来自顶端的Lgr 5+细胞产生显著更多的HC，并且具有显著更高的增殖和有丝分裂HC再生能力。接下来，我们使用微阵列分析来确定Lgr 5+祖细胞从顶端和基部的转录组表达谱。我们首先分析了Lgr 5+祖细胞中从顶端和基部富集和差异表达的基因。分析了Lgr 5+祖细胞增殖分化的细胞周期调控基因和转录因子。最后，为了进一步分析差异表达基因的作用，并获得耳蜗HC再生的基因网络的整体视图，我们创建了一个蛋白质-蛋白质相互作用网络。我们的数据集提示了可能调控Lgr 5+祖细胞增殖和HC再生能力的基因，这些基因可能为将来HC再生提供新的治疗靶点。
Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future.
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