Fig. 4: SFRP4⁺ stromal cells promote the proliferation of endometrial epithelial organoid in vitro through regenerative IGF1 signaling.

a Heatmap showed differentially expressed genes between SFRP4⁺ stromal cells and other stromal cell subsets. Among them, 15 secreted factors were significantly highly expressed in SFRP4⁺ stroma. b the transcriptional dataset (series: GSE4888) verified that the 15 secretory factors were specifically highly expressed in proliferative phase. c Venn diagram of genes significantly highly expressed in SFRP4⁺ stroma (light gray) compared to secretory factors (dark gray), and interaction clusters of ligands from SFRP4⁺ stroma to receptors from the proliferative epithelial subset (purple). d organoids culturing of endometrial epithelia cells cocultured with SFRP4⁺ stroma from normal or IGF1 knockdown (IGF1si-stroma) cells, scale bar, 200 μm. e quantification of endometrial epithelial organoids at different time points of co-cuture, **p < 0.01; f diameter of endometrial epithelial organoids at different time points of co-cuture, *p < 0.05. g organoids culturing of endometrial epithelia cells with or without IGF1 inhibitors when cocultured with SFRP4⁺ stroma, 4 IGF1 inhibitors (s1012, s1034, s1091, s1093) are from Selleck.cn, scale bar, 200 μm. h quantification of endometrial epithelial organoids in different groups of co-culture, **p < 0.01; ***p < 0.001. i diameter of endometrial epithelial organoids in different groups of co-cuture, **p < 0.01; ***p < 0.001.