Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells.

Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells.
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DOI:
10.1038/s41598-021-00273-y
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发表时间:
2021-10-22
期刊:
影响因子:
4.6
通讯作者:
Deng SX
Deng SX
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bonnet C;Oh D;Mei H;Robertson S;Chang D;Bourges JL;Behar-Cohen F;Zheng JJ;Deng SX

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角膜缘干细胞/祖细胞(LSCs)是一种非常小的生长在角膜缘的成体干细胞。几种Wnt配体,包括Wnt6,优先在边缘表达。为了研究Wnt6在体外LSC扩增条件下对人LSC增殖和维持的调节作用,我们制备了NIH-3T3饲养细胞,过表达不同水平的Wnt6。在表达Wnt6的3T3细胞上培养的LSCs的特性表明,高水平的Wnt6促进了LSCs的增殖。中等和高水平的Wnt6也增加了小细胞(直径≤12µm)的百分比,这是干细胞群体的一个特征。此外,在中高Wnt6水平下,表达分化标志物K12的细胞百分比显著降低。虽然Wnt6通常被认为是典型的Wnt配体,但我们的数据显示,在Wnt6补充的LSC培养中,典型和非典型Wnt信号通路被激活,这一发现表明,LSC调节需要两种通路之间的相互关系。
The corneal epithelium is consistently regenerated by limbal stem/progenitor cells (LSCs), a very small population of adult stem cells residing in the limbus. Several Wnt ligands, including Wnt6, are preferentially expressed in the limbus. To investigate the role of Wnt6 in regulating proliferation and maintenance of human LSCs in an in vitro LSC expansion setting, we generated NIH-3T3 feeder cells to overexpress different levels of Wnt6. Characterization of LSCs cultured on Wnt6 expressing 3T3 cells showed that high level of Wnt6 increased proliferation of LSCs. Medium and high levels of Wnt6 also increased the percentage of small cells (diameter ≤ 12 µm), a feature of the stem cell population. Additionally, the percentage of cells expressing the differentiation marker K12 was significantly reduced in the presence of medium and high Wnt6 levels. Although Wnt6 is mostly known as a canonical Wnt ligand, our data showed that canonical and non-canonical Wnt signaling pathways were activated in the Wnt6-supplemented LSC cultures, a finding suggesting that interrelationships between both pathways are required for LSC regulation.
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