Figure 4

Identification of key transcription factor (TFs) regulators during extravillous trophoblast cell differentiation. (a) Partition-based approximate graph abstraction (PAGA) analysis of EVT subpopulations, including column trophoblast cell (column EVT), interstitial extravillous trophoblast cells 1/2 (iEVT1/2), and endovascular extravillous trophoblast cells (enEVT). Lines show connections; line thickness corresponds to the level of connectivity (low (thin) to high (thick) PAGA connectivity). Heatmap showing min–max normalized expression of statistically significant (P < 0.001), dynamically variable TFs from pseudotime analysis for EVT trajectories. (b) The expression pattern of selected DEGs of column EVT, iEVT1 and enEVT. (c) Boxplot visualization of log-transformed, normalized expression of selected TFs in EVT subgroups. (d) Selected Gene Ontology (GO) terms of TFs differentially expressed in column EVT, iEVT1 and enEVT, respectively. (e) STRING database for the regulatory network analysis of selected TFs differentially expressed in column EVT, iEVT1 and enEVT. (f) Model of regulation loops of column EVT differentiation into enEVT. (g) Immunostaining of HLA-G, PRDM6 and HDAC1 in Mat_S of human full-term placenta. Scale bar represents 100 μm.