Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
J Matern Fetal Neonatal Med. 2024 Dec;37(1):2361278. doi: 10.1080/14767058.2024.2361278. Epub 2024 Jun 4.
Intrahepatic cholestasis of pregnancy (ICP) can cause adverse perinatal outcomes. Previous studies have demonstrated that the placenta of an ICP pregnancy differs in morphology and gene expression from the placenta of a normal pregnancy. To date, however, the genetic mechanism by which ICP affects the placenta is poorly understood. Therefore, the aim of this study was to investigate the differences in main cell types, gene signatures, cell ratio, and functional changes in the placenta between ICP and normal pregnancy.
Single-cell RNA sequencing (scRNA-seq) technology was used to detect the gene expression of all cells at the placental maternal-fetal interface. Two individuals were analyzed - one with ICP and one without ICP. The classification of cell types was determined by a graph-based clustering algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R software () function and DAVID website. The differentially expressed genes (DEGs) encoding transcription factors (TFs) were identified using getorf and DIAMOND software.
We identified 14 cell types and 22 distinct cell subtypes that showed unique functional properties. Additionally, we found differences in the proportions of fibroblasts 1, helper T (Th) cells, extravillous trophoblasts, and villous cytotrophoblasts, and we observed heterogeneity of gene expression between ICP and control placentas. Furthermore, we identified 263 DEGs that belonged to TF families, including zf-C2H2, HMGI/HMGY, and Homeobox. In addition, 28 imprinted genes were preferentially expressed in specific cell types, such as and in trophoblasts as well as and in fibroblasts.
Our results revealed the differences in cell-type ratios, gene expression, and functional changes between ICP and normal placentas, and heterogeneity was found among cell subgroups. Hence, the imbalance of various cell types affects placental activity to varying degrees, indicating the complexity of the cell networks that form the placental tissue system, and this alteration of placental function is associated with adverse events in the perinatal period.
妊娠肝内胆汁淤积症（ICP）可导致不良围产期结局。先前的研究表明，ICP 妊娠的胎盘在形态和基因表达上与正常妊娠的胎盘不同。然而，迄今为止，ICP 影响胎盘的遗传机制仍知之甚少。因此，本研究旨在探讨 ICP 和正常妊娠胎盘主要细胞类型、基因特征、细胞比例和功能变化的差异。
采用单细胞 RNA 测序（scRNA-seq）技术检测胎盘母胎界面所有细胞的基因表达。分析了 2 个人，一个患有 ICP，一个没有。细胞类型的分类通过基于图的聚类算法确定。使用 R 软件（）函数和 DAVID 网站进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。使用 getorf 和 DIAMOND 软件识别编码转录因子（TFs）的差异表达基因（DEGs）。
我们鉴定了 14 种细胞类型和 22 种独特的细胞亚型，这些细胞亚型具有独特的功能特性。此外，我们发现成纤维细胞 1、辅助性 T（Th）细胞、绒毛外滋养细胞和绒毛细胞滋养细胞的比例存在差异，并且我们观察到 ICP 和对照胎盘之间的基因表达存在异质性。此外，我们鉴定了 263 个属于 TF 家族的 DEGs，包括 zf-C2H2、HMGI/HMGY 和 Homeobox。此外，28 个印迹基因优先在特定细胞类型中表达，如滋养细胞中的和以及成纤维细胞中的和。
我们的结果揭示了 ICP 和正常胎盘之间细胞类型比例、基因表达和功能变化的差异，并且细胞亚群之间存在异质性。因此，各种细胞类型的失衡以不同程度影响胎盘活性，表明形成胎盘组织系统的细胞网络的复杂性，这种胎盘功能的改变与围产期不良事件有关。
