Single-Cell Chromatin Accessibility Landscape of Human Umbilical Cord Blood in Trisomy 18 Syndrome

Abstract Background: Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies.Results: In this study, we used the commercial Chromium platform (10x Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types without using antibodies. We set out to generate a single-cell atlas of chromatin accessibility in human umbilical cord blood from the healthy control donor and the 18 trisomy syndrome donor. Then, we carried out cell-type-specific gene regulatory network analysis at single-cell resolution of these differential accessibility-related loci genes and summarized the disease-related transcription factors (TFs) and target genes. Finally, we performed a cell-type-specific gene regulatory network analysis of these differential accessibility-related locus genes at single-cell resolution.Conclusions: Specifically, CCBN2 and MCM3 may be essential for the development of trisomy 18, and genes differentially expressed between the donor and patient were enriched in the human T-cell leukaemia virus 1 infection pathway. These screened disease-related transcription factors (TFs) and their target genes provide a basis for further research that will improve our understanding of trisomy 18 syndrome.