Characterization of Wnt and Notch-Responsive Lgr5+ Hair Cell Progenitors in the Striolar Region of the Neonatal Mouse Utricle.

Characterization of Wnt and Notch-Responsive Lgr5+ Hair Cell Progenitors in the Striolar Region of the Neonatal Mouse Utricle.
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新生小鼠子宫纹状体区 Wnt 和 Notch 响应性 Lgr5 毛细胞祖细胞的表征。

DOI:
10.3389/fnmol.2018.00137
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发表时间:
2018
影响因子:
4.8
通讯作者:
Li H
Li H
中科院分区:
医学2区
文献类型:
--
作者:
You D;Guo L;Li W;Sun S;Chen Y;Chai R;Li H

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听力和平衡功能障碍在很大程度上与毛细胞(HC)丧失有关。虽然在成年耳蜗中没有发生HC的再生,但在哺乳动物的椭圆体中,来自不同数量的支持细胞(SCs)的HC再生的能力仍然有限。作为对HC损伤的反应,这些Lgr5+干细胞,特别是纹状体区域的干细胞,可以再生HC。在本研究中,我们通过流式细胞术从转基因小鼠中分离出Lgr5+SCs和Plp1+SCs(分别来自纹状体和纹状体外区),以比较这两个SCs亚群的特性。我们发现Lgr5+祖细胞比Plp1+SCs具有更强的增殖和HC再生能力,Lgr5+祖细胞对Wnt和Notch信号的反应比Plp1+SCs更强。然后,我们通过RNA-Seq比较了两个群体的基因表达谱,发现了几个在两个群体中显著差异表达的基因,包括参与细胞周期、转录和细胞信号通路的基因。靶向这些基因和途径可能是激活HC再生的一种潜在方式。
Dysfunctions in hearing and balance are largely connected with hair cell (HC) loss. Although regeneration of HCs in the adult cochlea does not occur, there is still limited capacity for HC regeneration in the mammalian utricle from a distinct population of supporting cells (SCs). In response to HC damage, these Lgr5+ SCs, especially those in the striolar region, can regenerate HCs. In this study, we isolated Lgr5+ SCs and Plp1+ SCs (which originate from the striolar and extrastriolar regions, respectively) from transgenic mice by flow cytometry so as to compare the properties of these two subsets of SCs. We found that the Lgr5+ progenitors had greater proliferation and HC regeneration ability than the Plp1+ SCs and that the Lgr5+ progenitors responded more strongly to Wnt and Notch signaling than Plp1+ SCs. We then compared the gene expression profiles of the two populations by RNA-Seq and identified several genes that were significantly differentially expressed between the two populations, including genes involved in the cell cycle, transcription and cell signaling pathways. Targeting these genes and pathways might be a potential way to activate HC regeneration.
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