Lin28 Inhibits the Differentiation from Mouse Embryonic Stem Cells to Glial Lineage Cells through Upregulation of Yap1.
Lin28 Inhibits the Differentiation from Mouse Embryonic Stem Cells to Glial Lineage Cells through Upregulation of Yap1.
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DOI：
10.1155/2021/6674283
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发表时间：
2021
影响因子：
4.3
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Luo J;Zou H;Deng L;Sun X;Yuan P;Li P
RNA 结合蛋白 Lin28 独立于 let-7 microRNA 调节哺乳动物的神经胶质细胞生成。然而，具体的监管机制仍然不明确。在这里，我们建立了 Lin28a 或 Lin28b 过表达小鼠胚胎干细胞 (ESC)，发现这些细胞表达相似水平的核心多能因子，例如 Oct4 和 Sox2，并且与对照 ESC 相比，Yap1 增加，但谱系特异性标记物减少。这些 ESC 进一步分化为神经元和胶质细胞系细胞，结果表明 Lin28a/b 过表达不影响神经元标记物 βIII-微管蛋白的表达，但显着抑制胶质细胞系标记物，例如 Gfap 和 Mbp。有趣的是，Yap1 在小鼠 ESC 中的过度表达通过显示胶质细胞分化缺陷来表现出 Lin28a/b 过度表达的 ESC 的表型。用维替泊芬抑制 Yap1/Tead 介导的转录部分挽救了 Lin28a/b 过表达 ESC 的分化缺陷。从机制上讲，我们证明Lin28可以直接与Yap1 mRNA结合，并且Lin28a在mESC中对Yap1的诱导不依赖于Let7。综上所述，我们的结果揭示了 mESC 向胶质细胞谱系细胞分化过程中的一个新的 Lin28-Yap1 调控轴，这可能为体外胶质细胞的生成提供线索。
The RNA-binding protein Lin28 regulates neurogliogenesis in mammals, independently of the let-7 microRNA. However, the detailed regulatory mechanism remains obscured. Here, we established Lin28a or Lin28b overexpression mouse embryonic stem cells (ESCs) and found that these cells expressed similar levels of the core pluripotent factors, such as Oct4 and Sox2, and increased Yap1 but decreased lineage-specific markers compared to the control ESCs. Further differentiation of these ESCs to neuronal and glial lineage cells revealed that Lin28a/b overexpression did not affect the expression of neuronal marker βIII-tubulin, but dramatically inhibited the glial lineage markers, such as Gfap and Mbp. Interestingly, overexpression of Yap1 in mouse ESCs phenocopied Lin28a/b overexpression ESCs by showing defect in glial cell differentiation. Inhibition of Yap1/Tead-mediated transcription with verteporfin partially rescued the differentiation defect of Lin28a/b overexpression ESCs. Mechanistically, we demonstrated that Lin28 can directly bind to Yap1 mRNA, and the induction of Yap1 by Lin28a in mESCs is independent of Let7. Taken together, our results unravel a novel Lin28-Yap1 regulatory axis during mESC to glial lineage cell differentiation, which may shed light on glial cell generation in vitro.
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影响因子：
6
作者：
Robledinos-Antón N;Escoll M;Guan KL;Cuadrado A
通讯作者：
Cuadrado A
影响因子：
2.7
作者：
Moss, EG;Tang, LJ
通讯作者：
Tang, LJ
DOI：
10.1073/pnas.1220176110
发表时间：
2013-08-06
影响因子：
11.1
作者：
Cimadamore, Flavio;Amador-Arjona, Alejandro;Terskikh, Alexey V.
通讯作者：
Terskikh, Alexey V.
影响因子：
5.2
作者：
Morgado, Ana L.;Rodrigues, Cecilia M. P.;Sola, Susana
通讯作者：
Sola, Susana
影响因子：
4.4
作者：
Dehghanian, Fariba;Hojati, Zohreh;Masoudi-Nejad, Ali
通讯作者：
Masoudi-Nejad, Ali