Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window

摘要

Schematic representation of in vitro time-course experiment. -SNE projection of 4580 EnSC, colour-coded according to days of decidualization (D0-8) and upon withdrawal (WD) of the differentiation signal for 48 h. D0 represents undifferentiated EnSC. The same -SNE plot now colour-coded according to transcriptional state (S1–7). Violin plots showing log-transformed, normalized expression levels for indicated genes in decidual cells (DC, state S5) and senescent decidual cells (snDC, state S6). Relative proportion of total cells assigned to states S5 (DC), S6 (snDC) and S7 at each experimental timepoint. Decidualizing EnSC were placed in pseudotime to reconstruct the trajectory of differentiation, revealing a continuous trajectory towards senescence with a single branch point marking the divergence of DC. Heatmap showing gene dynamics during cell state transition at the branch point shown in panel ( ). Columns are points in pseudotime while rows represent the 50 most dynamic genes at the branch point. The beginning of pseudotime is in the middle of the heatmap and the trajectory towards DC and snDC are indicated by the arrows. Hierarchical clustering visualizes modules of genes with similar lineage-dependent expression patterns.