Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, 230601, PR China.
Anhui Provincial Hospital, First Affiliated Hospital of University of Science and Technology of China, Hefei, 230001, China.
Biochem Biophys Res Commun. 2021 May 7;552:142-149. doi: 10.1016/j.bbrc.2021.03.030. Epub 2021 Mar 19.
Fully understanding the regulatory network under the pluripotency of embryonic stem cells (ESC) is a prerequisite for their safe application. Here, we addressed the characteristics of metastasis-associated (MTA) family members in human ESCs and found that knockdown of the expression of MTA2 and MTA3, but not MTA1, would induce differentiation. High-throughput sequence and quantitative real-time PCR showed that the decreased MTA2 or MTA3 gene transcript mainly led to the emergence of mesendoderm associated markers. Finally, based on the chemical small molecule library screening, we observed that addition of ID8, a specific inhibitor of the dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), was able to impair the differentiation phenotype induced by MTA2 and MTA3 reduction. Functional assay showed that ID8 could mediate differentiation caused by MTA2 or MTA3 knockdown mainly through inhibition of DYRK4 activity. Therefore, our finding provides the evidence that the functions of MTA family genes in human ESCs are different. Revealing the function of MTA in ESCs with different pluripotency states will help us better understand and apply stem cells.
充分了解胚胎干细胞（ESC）多能性的调控网络是其安全应用的前提。在这里，我们研究了人 ESC 中转移相关（MTA）家族成员的特征，发现下调 MTA2 和 MTA3 的表达，而不是 MTA1，会诱导分化。高通量测序和定量实时 PCR 显示，MTA2 或 MTA3 基因转录本的减少主要导致中胚层相关标记物的出现。最后，基于化学小分子文库筛选，我们观察到添加 ID8（双特异性酪氨酸磷酸化调节激酶（DYRKs）的特异性抑制剂）能够破坏由 MTA2 和 MTA3 减少引起的分化表型。功能测定表明，ID8 可以通过抑制 DYRK4 的活性来介导由 MTA2 或 MTA3 敲低引起的分化。因此，我们的发现提供了证据，证明 MTA 家族基因在人 ESC 中的功能是不同的。揭示不同多能状态下的 MTA 在 ESC 中的功能将有助于我们更好地理解和应用干细胞。
