Albers Renee E, Selesniemi Kaisa, Natale David R C, Brown Thomas L
Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435, USA.
Department of Reproductive Medicine, University of California-San Diego, San Diego, California 92093, USA.
Int J Stem Cells. 2018 May 30;11(1):111-120. doi: 10.15283/ijsc17069.
Transforming growth factor beta (TGF-) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-. However, the signal transduction pathway activated by TGF- to induce SM10 progenitor differentiation has yet to be fully investigated.
In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF- induced differentiation. Activation of the TGF- pathway and the ability of TGF- to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis.
In this report, we show that three isoforms of TGF- have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF- superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF- induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.
转化生长因子β（TGF-β）信号已被证明可控制大量关键的细胞活动，如细胞死亡、分化和发育，并且被认为是胎盘功能的主要调节因子。SM10细胞是一种小鼠胎盘祖细胞系，先前已证明在用TGF-β处理后可分化为营养转运的、类似迷路的细胞。然而，TGF-β激活以诱导SM10祖细胞分化的信号转导途径尚未得到充分研究。
在本研究中，使用SM10迷路祖细胞系来研究TGF-β诱导的分化。通过光学显微镜、荧光素酶测定和蛋白质印迹分析来研究TGF-β途径的激活以及TGF-β诱导分化的能力。
在本报告中，我们表明TGF-β的三种异构体具有使SM10细胞终末分化的能力，而TGF-β超家族的其他主要成员，Nodal和激活素A则没有。此外，我们已经确定TGF-β诱导的Smad2磷酸化可通过ALK-5受体介导，随后激活素反应元件发生反式激活。我们的研究确定了SM10祖细胞中一条重要的调节信号通路，该通路参与迷路滋养层细胞的分化。
