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. 2018 Mar 13;9:1056. doi: 10.1038/s41467-018-03348-z

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — CXCL12β discriminates CAF-S1 and CAF-S4 cells. a PCA based on the 500 most variant transcripts differentiating CAF-S1 (red) and CAF-S4 (blue). b HC (500 most variant transcripts) using Ward’s method with Euclidean distances. Each column represents a CAF subset and each row a gene. Color saturation shows gene expression deviation from the mean (above in red, below in blue). c Venn diagram showing overlap between mesenchymal signature (defined in ref. ⁷) and CAF-S1 signature (Supplementary Data 1). P value is from hypergeometric test. d Scatter plots of CXCL12α (NM_000609) or CXCL12β (NM_199168) mRNA levels in CAF-S1 and CAF-S4 subsets. e, f Venn diagrams showing overlap between genes correlated or anti-correlated with CXCL12β (e) or CXCL12α (f) and CAF-S1 or CAF-S4 signatures (Supplementary Data 1 and 2). P values are from hypergeometric test. g Kaplan−Meier curves of overall survival according to low- and high-CXCL12β mRNA levels (N = 53 in low-CXCL12β subgroup and N = 54 patients in high-CXCL12β subgroup, Institut Curie). P value is based on log-rank test. h Scatter plots showing CXCL12β mRNA levels in mesenchymal and non-mesenchymal HGSOC from the Institut Curie, AOCS, and TCGA cohorts. Data (log2 of probeset (203666_at) intensity) are shown as mean ± SEM. P values are from Mann-Whitney test. i Scatter plot showing ratio of CXCL12α and CXCL12β expression levels in mesenchymal and non-mesenchymal HGSOC of the Institut Curie cohort. Data are shown as mean ± SEM. P values are from Mann-Whitney test. j, k Representative views of CXCL12 (j) and CXCR4 (k) immunostaining in HGSOC. Scale bar, 50 μm (low magnification) and 20 μm (inset). l Scatter plots showing histological scores (H score) of CXCL12 and CXCR4 proteins. H score corresponds to the percentage of positive cells (in CAF and at epithelial cell surface, arrows in j, k) multiplied by the staining intensity. Data are shown as mean ± SEM. P values are from Mann-Whitney test. m Representative view of CXCL12 mRNA detected in fibroblasts by in situ hybridization, using RNAscope^® Technology on HGSOC tissue section. Scale bar, 20 μm (low magnification) and 6 μm (inset)