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Fig 1.

Classification of single-cell subpopulations of EC and identification of marker genes.

(A) UMAP plot of annotated cell types in EC; (B) Bubble plot showing gene expression in six cell clusters; (C) Violin plot showing marker gene expression in EC cell subpopulations; (D) Percentage of each cell subpopulation within all samples (5 patients with EC); (E) Demonstration of the percentage of each subpopulation in EC cell samples.

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Fig 1 Expand

Fig 2.

Relationship of different cell clusters of EC to estrogen signaling pathways.

(A-B) Differences in enrichment scores for estrogen signaling pathways in different cell subpopulations based on the AddModuleScore function (A) and AUCell package (B); (C) Distribution of three key estrogenic pathways and cell proliferation-promoting genes (including ESR1, CCND1, and CDKN1A) in the EC.

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Fig 3.

Response of epithelial cells to estrogen in the EC.

(A) UMAP showed classification into 5 cell subpopulations based on 7,162 epithelial cells; (B) Comparison of the level of early activation of five epithelial cell subpopulations in response to estrogen; (C) Differential expression of estrogen-related gene levels in different epithelial cell subpopulations; (D) Demonstration of enrichment analysis of biological processes of genes in Epi cluster1; (E-F) Distribution of MUC1 (E) and ELF3 (F) genes in EC tissues.

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Fig 4.

Response of fibroblasts to estrogen in the EC.

(A) UMAP showed classification into 7 cell subpopulations based on 16,019 fibroblasts; (B) Comparison of the level of early activation of seven fibroblast subpopulations in response to estrogen; (C) Differential expression of estrogen-related gene levels in different fibroblast subpopulations; (D) Demonstration of enrichment analysis of biological processes of genes in Fib cluster3; (E-F) Distribution of B4GALT1 (E) and XBP1 (F) genes in EC tissues.

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Fig 5.

Response of endothelial cells to estrogen in the EC.

(A) UMAP showed classification into 4 cell subpopulations based on 3,740 endothelial cells; (B) Comparison of the level of early activation of four endothelial cell subpopulations in response to estrogen; (C) Differential expression of estrogen-related gene levels in different endothelial cell subpopulations; (D) Demonstration of enrichment analysis of biological processes of genes in Endo cluster3; (E-F) Distribution of B4GALT1 (E) and SLC2A1 (F) genes in EC tissues.

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Fig 6.

Identification of biomarkers of early response to estrogen in EC.

(A) Screening of DEGs between cell subpopulations (including Epi cluster1, Fib cluster3, and Endo cluster3); (B) Screening of cellular subpopulations for DEGs as well as Stage I and para-cancer tissue genes in EC to identify diagnostic markers; (C) Expression levels of 24 early diagnostic markers of estrogen response in EC and its para-cancer tissues.

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Fig 7.

Predictive modeling of early diagnostic markers of estrogen response in EC.

(A-F) Receiver operating characteristic of logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), eXtreme gradient boosting (XGB), and neural network (NK).

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Fig 7 Expand