International Genome Center, Jiangsu University, Zhenjiang 212013, China.
Changzhou Maternal and Child Health Care Hospital, Nanjing Medical University, Changzhou 213000, China.
Mol Cells. 2022 May 31;45(5):317-328. doi: 10.14348/molcells.2021.0211.
Trophoblasts, important functional cells in the placenta, play a critical role in maintaining placental function. The heterogeneity of trophoblasts has been reported, but little is known about the trophoblast subtypes and distinctive functions during preeclampsia (PE). In this study, we aimed to gain insight into the cell type-specific transcriptomic changes by performing unbiased single-cell RNA sequencing (scRNA-seq) of placental tissue samples, including those of patients diagnosed with PE and matched healthy controls. A total of 29,006 cells were identified in 11 cell types, including trophoblasts and immune cells, and the functions of the trophoblast subtypes in the PE group and the control group were also analyzed. As an important trophoblast subtype, extravillous trophoblasts (EVTs) were further divided into 4 subgroups, and their functions were preliminarily analyzed. We found that some biological processes related to pregnancy, hormone secretion and immunity changed in the PE group. We also identified and analyzed the regulatory network of transcription factors (TFs) identified in the EVTs, among which 3 modules were decreased in the PE group. Then, through cell experiments, we found that in one of the modules, CEBPB and GTF2B may be involved in EVT dysfunction in PE. In conclusion, our study showed the different transcriptional profiles and regulatory modules in trophoblasts between placentas in the control and PE groups at the single-cell level; these changes may be involved in the pathological process of PE, providing a new molecular theoretical basis for preeclamptic trophoblast dysfunction.
滋养细胞是胎盘的重要功能细胞，在维持胎盘功能方面起着关键作用。已经报道了滋养细胞的异质性，但对于子痫前期（PE）中滋养细胞亚型和独特功能知之甚少。在这项研究中，我们旨在通过对包括被诊断为 PE 和匹配的健康对照组的胎盘组织样本进行无偏单细胞 RNA 测序（scRNA-seq），深入了解细胞类型特异性转录组变化。在 11 种细胞类型中鉴定出了 29,006 个细胞，包括滋养细胞和免疫细胞，并分析了 PE 组和对照组中滋养细胞亚型的功能。作为一种重要的滋养细胞亚型，绒毛外滋养细胞（EVT）进一步分为 4 个亚群，初步分析了它们的功能。我们发现 PE 组中一些与妊娠、激素分泌和免疫相关的生物学过程发生了变化。我们还鉴定和分析了 EVT 中鉴定的转录因子（TFs）的调控网络，其中 3 个模块在 PE 组中减少。然后，通过细胞实验，我们发现其中一个模块中，CEBPB 和 GTF2B 可能参与了 PE 中 EVT 的功能障碍。总之，我们的研究在单细胞水平上显示了对照组和 PE 组胎盘滋养细胞之间不同的转录谱和调控模块；这些变化可能与 PE 的病理过程有关，为子痫前期滋养细胞功能障碍提供了新的分子理论基础。
