Human placental development during early pregnancy is poorly understood. Many conceptuses are lost at this stage. It is thought that preeclampsia, intrauterine growth restriction and other placental syndromes that manifest later in pregnancy may originate early in placentation. Thus, there is a need for models of early human placental development. Treating human embryonic stem cells (hESCs) with BMP4 (bone morphogenic protein 4) plus A83-01 (ACTIVIN/NODAL signaling inhibitor) and PD173074 (fibroblast growth factor 2 or FGF2 signaling inhibitor) (BAP conditions) induces differentiation to the trophoblast lineage (hESC_BAP), but it is not clear which stage of trophoblast differentiation these cells resemble. Here, comparison of the hESC_BAP transcriptome to those of trophoblasts from human blastocysts, trophoblast stem cells and placentas collected in the first–third trimester of pregnancy by principal component analysis suggests that hESC after 8 days BAP treatment most resemble first trimester syncytiotrophoblasts. To further test this hypothesis, transcripts were identified that are expressed in hESC_BAP but not in cultures of trophoblasts isolated from term placentas. Proteins encoded by four genes, GABRP (gamma-aminobutyric acid type A receptor subunit Pi), WFDC2 (WAP four-disulfide core domain 2), VTCN1 (V-set domain containing T-cell activation inhibitor 1) and ACTC1 (actin alpha cardiac muscle 1), immunolocalized to placentas at 4–9 weeks gestation, and their expression declined with gestational age (R² = 0.61–0.83). None are present at term. Expression was largely localized to syncytiotrophoblast of both hESC_BAP cells and placental material from early pregnancy. WFDC2, VTCN1 and ACTC1 have not previously been described in placenta. These results support the hypothesis that hESC_BAP represent human trophoblast analogous to that of early first trimester and are a tool for discovery of factors important to this stage of placentation.

中文翻译：

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使用人类胚胎干细胞模型发现 GABRP、WFDC2、VTCN1 和 ACTC1 作为早期早期人类滋养层细胞的标志物。

人们对妊娠早期的胎盘发育知之甚少。许多概念在这个阶段丢失了。人们认为，先兆子痫、宫内发育迟缓和其他妊娠后期出现的胎盘综合征可能起源于胎盘早期。因此，需要早期人类胎盘发育模型。用 BMP4（骨形态发生蛋白 4）加 A83-01（ACTIVIN/NODAL 信号抑制剂）和 PD173074（成纤维细胞生长因子 2 或 FGF2 信号抑制剂）（BAP 条件）处理人胚胎干细胞 (hESCs) 诱导分化为滋养层细胞谱系。 hESC _BAP），但尚不清楚这些细胞类似于滋养层分化的哪个阶段。在这里，比较 hESC _BAP通过主成分分析从人类囊胚、滋养层干细胞和胎盘收集到的滋养层细胞的转录组表明，BAP 治疗 8 天后的 hESC 最类似于孕早期合体滋养层细胞。为了进一步检验这一假设，鉴定了在 hESC _BAP中表达但不在足月胎盘分离的滋养细胞培养物中表达的转录本。由四个基因编码的蛋白质，GABRP（γ-氨基丁酸 A 型受体亚基 Pi）、WFDC2（WAP 四二硫键核心域 2）、VTCN1（包含 T 细胞激活抑制剂 1 的 V 组域）和ACTC1（肌动蛋白 α 心肌 1），在妊娠 4-9 周时免疫定位于胎盘，并且它们的表达随着胎龄而下降（R ² = 0.61-0.83）。没有人在场。表达主要集中在 hESC _BAP细胞和早孕胎盘材料的合体滋养层细胞中。WFDC2、VTCN1 和 ACTC1 以前没有在胎盘中被描述过。这些结果支持以下假设：hESC _BAP代表类似于早孕早期的人类滋养层，并且是发现对胎盘形成这一阶段重要的因素的工具。