A function of fascin1 in the colony formation of mouse embryonic stem cells
A function of fascin1 in the colony formation of mouse embryonic stem cells
复制标题
DOI：
10.1002/stem.3197
复制
发表时间：
2020-06-01
期刊：
影响因子：
5.2
通讯作者：
Feng, Xi-Qiao
中科院分区：
文献类型：
--
作者：
Fan, Yan-Lei;Li, Bo;Feng, Xi-Qiao
已知 Fascin1 通过与肌动蛋白丝结合来参与癌细胞的迁移。最近的研究证明，Fascin1 还可以调节癌症干细胞中肿瘤发生和多能性基因的维持等过程。然而，Fascin1 在胚胎干细胞中的功能仍不清楚。在本文中，我们报道了fascin1在小鼠胚胎干细胞（mESC）中高表达并广泛分布，并受到JAK-STAT3和β-catenin的调节。我们发现，fascin1的过度表达通过细胞间粘附分子的下调来损害mESC集落的形成，并且模拟fascin1的去磷酸化突变或用Go6983抑制磷酸化可显着增强集落形成。过度磷酸化的fascin1可以通过核定位和抑制DNA甲基转移酶的表达来促进mESCs多能性的维持。我们的研究结果证明了fascin1作为重要调节因子在mESC集落形成和多能性中的新功能，并为胚胎干细胞体外自组织和发育的分子机制提供了见解。
Fascin1 is known to participate in the migration of cancer cells by binding to actin filaments. Recent studies evidenced that fascin1 also modulates processes such as the tumorigenesis and maintenance of pluripotency genes in cancer stem cells. However, the function of fascin1 in embryonic stem cells remains unclear. In this paper, we report that fascin1 is highly expressed and widely distributed in mouse embryonic stem cells (mESCs), which are regulated by JAK-STAT3 and beta-catenin. We found that the overexpression of fascin1 impairs the formation of mESC colonies via the downregulation of intercellular adhesion molecules, and that mimicking the dephosphorylated mutation of fascin1 or inhibiting phosphorylation with Go6983 significantly enhances colony formation. Hyperphosphorylated fascin1 can promote the maintenance of pluripotency in mESCs via nuclear localization and suppressing DNA methyltransferase expression. Our findings demonstrate a novel function of fascin1, as a vital regulator, in the colony formation and pluripotency of mESCs and provide insights into the molecular mechanisms underlying embryonic stem cell self-organization and development in vitro.