Sahgal Namita, Canham Lindsey N, Konno Toshihiro, Wolfe Michael W, Soares Michael J
Department of Pathology & Laboratory Medicine, Division of Cancer & Developmental Biology, Institute of Maternal-Fetal Biology, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Differentiation. 2005 Dec;73(9-10):452-62. doi: 10.1111/j.1432-0436.2005.00044.x.
Trophoblast giant cells are located at the maternal-embryonic interface and have fundamental roles in the invasive and endocrine phenotypes of the rodent placenta. In this report, we describe the experimental modulation of trophoblast stem cell and trophoblast giant cell phenotypes using the Rcho-1 trophoblast cell model. Rcho-1 trophoblast cells can be manipulated to proliferate or differentiate into trophoblast giant cells. Differentiated Rcho-1 trophoblast cells are invasive and possess an endocrine phenotype, including the production of members of the prolactin (PRL) family. Dimethyl sulfoxide (DMSO), a known differentiation-inducing agent, was found to possess profound effects on the in vitro development of trophoblast cells. Exposure to DMSO, at non-toxic concentrations, inhibited trophoblast giant cell differentiation in a dose-dependent manner. These concentrations of DMSO did not significantly affect trophoblast cell proliferation or survival. Trophoblast cells exposed to DMSO exhibited an altered morphology; they were clustered in tightly packed colonies. Trophoblast giant cell formation was disrupted, as was the expression of members of the PRL gene family. The effects of DMSO were reversible. Removal of DMSO resulted in the formation of trophoblast giant cells and expression of the PRL gene family. The phenotype of the DMSO-treated cells was further determined by examining the expression of a battery of genes characteristic of trophoblast stem cells and differentiated trophoblast cell lineages. DMSO treatment had a striking stimulatory effect on eomesodermin expression and a reciprocal inhibitory effect on Hand1 expression. In summary, DMSO reversibly inhibits trophoblast differentiation and induces a quiescent state, which mimics some but not all aspects of the trophoblast stem cell phenotype.
滋养层巨细胞位于母胎界面，在啮齿动物胎盘的侵袭和内分泌表型中发挥着重要作用。在本报告中，我们描述了使用Rcho-1滋养层细胞模型对滋养层干细胞和滋养层巨细胞表型进行的实验性调控。Rcho-1滋养层细胞可以被操控以增殖或分化为滋养层巨细胞。分化后的Rcho-1滋养层细胞具有侵袭性，并具有内分泌表型，包括催乳素（PRL）家族成员的产生。二甲基亚砜（DMSO）是一种已知的诱导分化剂，被发现对滋养层细胞的体外发育具有深远影响。在无毒浓度下暴露于DMSO会以剂量依赖的方式抑制滋养层巨细胞的分化。这些浓度的DMSO对滋养层细胞的增殖或存活没有显著影响。暴露于DMSO的滋养层细胞表现出形态改变；它们聚集成紧密堆积的集落。滋养层巨细胞的形成受到破坏，PRL基因家族成员的表达也受到破坏。DMSO的作用是可逆的。去除DMSO会导致滋养层巨细胞的形成和PRL基因家族的表达。通过检测一系列滋养层干细胞和分化的滋养层细胞谱系特征基因的表达，进一步确定了DMSO处理细胞的表型。DMSO处理对中胚层决定因子的表达有显著的刺激作用，对Hand1的表达有相反的抑制作用。总之，DMSO可逆地抑制滋养层分化并诱导静止状态，这模拟了滋养层干细胞表型的一些但不是所有方面。
