Pook Martin, Teino Indrek, Kallas Ade, Maimets Toivo, Ingerpuu Sulev, Jaks Viljar
Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Riia 23, 51010, Estonia.
Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Riia 23, 51010, Estonia; Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83, Huddinge, Sweden.
PLoS One. 2015 Sep 17;10(9):e0138346. doi: 10.1371/journal.pone.0138346. eCollection 2015.
Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain-145 kDa-accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation.
层粘连蛋白异构体层粘连蛋白-511和-521由人胚胎干细胞(hESC)表达,可作为生长基质在多能条件下培养这些细胞。然而,这些层粘连蛋白在hESC分化诱导过程中的表达尚未得到详细研究。此外,关于分化中的hESC中层粘连蛋白链表达模式的数据也很稀少。在本研究中,我们旨在填补这一空白,研究视黄酸(RA)诱导hESC早期分化过程中层粘连蛋白表达的潜在变化。我们发现,在hESC分化的早期阶段,层粘连蛋白-511而非-521在定向细胞中积累。我们还对层粘连蛋白链谱进行了全面分析,发现多能hESC表达的层粘连蛋白链种类比以前显示的更多样化。特别是,我们提供的证据表明,除了α1、α5、β1、β2和γ1链外,hESC还表达α2、α3、β3、γ2和γ3链蛋白及mRNA。此外,我们发现层粘连蛋白α3链的一个变体——145 kDa——在RA处理的hESC中积累,表明这些细胞在分化早期主要产生α3链的特异性修饰版本。