The Expression and Roles of the Super Elongation Complex in Mouse Cochlear Lgr5+ Progenitor Cells.

The Expression and Roles of the Super Elongation Complex in Mouse Cochlear Lgr5+ Progenitor Cells.
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DOI:
10.3389/fncel.2021.735723
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发表时间:
2021
影响因子:
5.3
通讯作者:
Chai R
Chai R
中科院分区:
医学2区
文献类型:
--
作者:
Chen Y;Qiang R;Zhang Y;Cao W;Wu L;Jiang P;Ai J;Ma X;Dong Y;Gao X;Li H;Lu L;Zhang S;Chai R

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超延伸复合物(SEC)在小鼠胚胎干细胞的增殖和分化中起着重要作用。然而,SEC在内耳中的表达模式和功能尚未研究。在这里,我们研究了三个关键的SEC组分,AFF1,AFF4和ELL3的内耳表达模式,发现这三种蛋白质都在耳蜗毛细胞(HC)和支持细胞(SC)中表达。我们还在SEC抑制剂flavopiridol存在下体外培养Lgr5+内耳祖细胞用于球体形成测定和分化测定。我们发现flavopiridol处理降低了Lgr5+祖细胞的增殖能力,而Lgr5+祖细胞的分化能力不受影响。我们的研究结果表明,SEC可能在调节内耳祖细胞,从而调节HC再生中发挥重要作用。因此,深入研究SEC信号通路在内耳中的具体作用,对开发感音神经性耳聋的有效治疗方法具有重要意义。
The super elongation complex (SEC) has been reported to play a key role in the proliferation and differentiation of mouse embryonic stem cells. However, the expression pattern and function of the SEC in the inner ear has not been investigated. Here, we studied the inner ear expression pattern of three key SEC components, AFF1, AFF4, and ELL3, and found that these three proteins are all expressed in both cochlear hair cells (HCs)and supporting cells (SCs). We also cultured Lgr5+ inner ear progenitors in vitro for sphere-forming assays and differentiation assays in the presence of the SEC inhibitor flavopiridol. We found that flavopiridol treatment decreased the proliferation ability of Lgr5+ progenitors, while the differentiation ability of Lgr5+ progenitors was not affected. Our results suggest that the SEC might play important roles in regulating inner ear progenitors and thus regulating HC regeneration. Therefore, it will be very meaningful to further investigate the detailed roles of the SEC signaling pathway in the inner ear in vivo in order to develop effective treatments for sensorineural hearing loss.
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