Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy [placenta-ncbi-cell-line_scRNA-seq_snRNA-seq]. Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy [placenta-ncbi-cell-line_scRNA-seq_snRNA-seq]

The human placenta plays vital roles in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, however, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here, we conducted integrated snRNA-seq and snATAC-seq on human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their presence in human trophoblast stem cells (hTSCs)-derived STB. Furthermore, we identified transcription factor (TF) motifs that are biased towards diverse STB nuclear lineages through their associated gene regulatory networks. The role of these TFs in STB differentiation were confirmed in the hTSCs- and trophoblast organoid-derived STB. Together, our data provide valuable insights into the heterogeneity of human STB and represents a valuable resource for interpreting its associated pregnancy complications. Overall design: To determine multinucleated STB features in vitro, two hTSC cell lines, which were derived from either human early blastocyst (hereinafter referred as hTSCs-BL) and or first-trimester placental CTBs (hereinafter referred as hTSCs-CT30), were cultured and differentiated to STB. we conducted snRNA-seq analysis of STB derived from both hTSCs-BL and hTSCs-CT30, along with scRNA-seq sequencing for the two hTSCs.