Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta
Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta
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DOI：
10.1093/biolre/ioy042
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发表时间：
2018-08-01
影响因子：
3.6
通讯作者：
Illsley, Nicholas P.
中科院分区：
文献类型：
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作者：
DaSilva-Arnold, Sonia C.;Zamudio, Stacy;Illsley, Nicholas P.
妊娠早期人类胎盘细胞滋养细胞（CTB）从依赖于锚定的上皮表型分化为间充质样侵袭性上皮外滋养细胞（EVT），这对母胎界面的发育至关重要。我们之前的研究表明，妊娠早期CTB向EVT的分化涉及上皮-间质转化（EMT）。在这里，我们比较了正常妊娠晚期胎盘或前置胎盘与异常侵入性胎盘（AIP）衍生的CTB和EVT的上皮间质特征。从剖宫产术后正常足月胎盘或前置胎盘中分离CTB和EVT，从剖宫产术后AIP中分离EVT。通过测定细胞角蛋白-7和HLA-G来验证细胞的身份。将正常足月CTB与正常足月胎盘或前置胎盘的EVT进行比较，对与EMT相关的基因进行差异表达分析，发现70%的被检测基因发生了变化。虽然显示出与CTB相关的间充质表型，但妊娠晚期EVT的许多基因表达变化相对于妊娠早期EVT减少。我们认为，与妊娠早期相比，妊娠晚期EVT处于更受约束的亚稳态。相比之下，AIP的EVT表现出比正常妊娠晚期EVT更多的间充质特征，使其在EMT谱上更接近妊娠早期EVT，与更具侵袭性的表型一致。来自异常侵袭性胎盘的外滋养细胞比正常妊娠晚期的细胞表现出更多的间充质特征，与过度侵袭表型一致。
Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchorage-dependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal-fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP). CTB and EVT were isolated from normal term placenta or placenta previa following Caesarean section and EVT from AIP following Caesarean hysterectomy. Cell identity was validated by measurement of cytokeratin-7 and HLA-G. Comparing normal term CTB with EVT from normal term placenta or placenta previa for differential expression analysis of genes associated with the EMT showed changes in > 70% of the genes probed. While demonstrating a mesenchymal phenotype relative to CTB, many of the gene expression changes in third trimester EVT were reduced relative to the first trimester EVT. We suggest that third trimester EVT are in a more constrained, metastable state compared to first trimester equivalents. By contrast, EVT from AIP demonstrate characteristics that are more mesenchymal than normal third trimester EVT, placing them closer to first trimester EVT on the EMT spectrum, consistent with a more invasive phenotype.Summary SentenceExtravillous trophoblast cells from abnormally invasive placenta demonstrate more mesenchymal characteristics than normal third trimester cells, consistent with an overinvasive phenotype.