Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua 8370993, Chile.
Int J Mol Sci. 2022 Oct 6;23(19):11873. doi: 10.3390/ijms231911873.
Umbilical and placental vessels and endothelial cells (EC) are common models to study placental function and vascular programming. Arterio-venous differences are present in the umbilical endothelium; however, the heterogeneity of small placental vessels and the expression of potential micro- vs. macro-vascular (MMV) markers are poorly described. Here, we performed a meta-analysis of transcriptomic and DNA methylation data from placental and umbilical EC. Expression and methylation profiles were compared using hierarchical clustering, dimensionality reduction (i.e., tSNE, MDS, and PHATE), and enrichment analysis to determine the occurrence of arterio-venous (AVH) and micro-macro heterogeneity (MMH). CpG sites correlated with gene expression of transcriptional markers of MMH and AVH were selected by Lasso regression and used for EC discrimination. General transcriptional profile resulted in clear segregation of EC by their specific origin. MM and AVH grouping were also observed when microvascular markers were applied. Altogether, this meta-analysis provides cogent evidence regarding the transcriptional and epigenomic profiles that differentiate among EC, proposing novel markers to define phenotypes based on MM levels.
脐带和胎盘血管及内皮细胞（EC）是研究胎盘功能和血管发育的常用模型。脐带内皮中存在动静脉差异；然而，小胎盘血管的异质性以及潜在的微-大血管（MMV）标志物的表达情况描述甚少。在这里，我们对来自胎盘和脐带 EC 的转录组学和 DNA 甲基化数据进行了荟萃分析。使用层次聚类、降维（即 tSNE、MDS 和 PHATE）和富集分析比较表达和甲基化谱，以确定动静脉（AVH）和微-大异质性（MMH）的发生情况。通过lasso 回归选择与 MMH 和 AVH 转录标志物基因表达相关的 CpG 位点，并用于 EC 鉴别。一般转录谱可根据其特定来源清楚地区分 EC。当应用微血管标志物时，也观察到 MM 和 AVH 分组。总的来说，这项荟萃分析为区分 EC 的转录组和表观基因组图谱提供了有力证据，提出了基于 MM 水平定义表型的新标志物。
