Department of Engineering Mechanics, Institute of Biomechanics and Medical Engineering, AML, Tsinghua University, Beijing, People's Republic of China.
Stem Cells. 2020 Sep;38(9):1078-1090. doi: 10.1002/stem.3197. Epub 2020 Jun 1.
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 article, we report that fascin1 is highly expressed and widely distributed in mouse embryonic stem cells (mESCs), which are regulated by JAK-STAT3 and β-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 Gö6983 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.
Fascin1 已知通过与肌动蛋白丝结合参与癌细胞的迁移。最近的研究表明，Fascin1 还调节了肿瘤发生和癌症干细胞中多能性基因的维持等过程。然而，Fascin1 在胚胎干细胞中的功能尚不清楚。在本文中，我们报道 Fascin1 在小鼠胚胎干细胞（mESC）中高度表达且广泛分布，其受 JAK-STAT3 和 β-catenin 调控。我们发现，通过下调细胞间黏附分子，Fascin1 的过表达会损害 mESC 集落的形成，而模拟 Fascin1 的去磷酸化突变或用 Gö6983 抑制磷酸化可显著增强集落形成。高磷酸化 Fascin1 可通过核定位和抑制 DNA 甲基转移酶表达来促进 mESC 的多能性维持。我们的研究结果表明 Fascin1 作为一个重要的调节因子，在 mESC 的集落形成和多能性中具有新的功能，并为胚胎干细胞自我组织和体外发育的分子机制提供了新的见解。
