ABSTRACT
During pregnancy the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy , Female , Humans , COVID-19/genetics , Transcriptome , SARS-CoV-2 , Epigenomics , Pregnancy Complications, Infectious/genetics , Single-Cell AnalysisABSTRACT
Chronic inflammatory diseases (CIDs) have complex pathologies that result from aberrant and persistent immune responses. However, the precise triggers and mechanisms remain elusive. An important aspect of CID research focuses on epigenetics modifications, which regulate gene expression and provide a dynamic transcriptional response to inflammation. In recent years, mounting evidence has demonstrated an association between epigenomic and transcriptomic dysregulation and the phenotypes of CIDs. In particular, epigenetic changes at cis-regulatory elements have provided new insights for immune cell-specific alterations that contribute to disease etiology. Furthermore, the advancements in single-cell genomics provide novel solutions to cell type heterogeneity, which has long posed challenges for CID diagnosis and treatment. In this review, we discuss the current state of epigenomics research of CID and the insights derived from single-cell transcriptomic and epigenomic studies.