Fig. 6

Contextualizing the CD105⁺ fibroblast signature. A and B scGSEA was performed on fibroblasts from a scRNA-seq dataset [28] using a custom gene list comprised of the top 30 gene differentially expressed in CD105⁺ fibroblasts (Fig. 2B), standardized mean difference: small effect size (0.2–0.5) *, medium effect size (0.5–0.8) **, large effect size (> 0.8) ***. A Split by fibroblast subtype. B Fibroblasts split by menopausal status. C CellChat was used to infer number and strength of interactions between different cell subtypes from pre and postmenopausal women [28]. D (left panel) Representative fluorescent image (20X objective) of DNA (Hoechst, blue), KRT19 (K19, green), KRT14 (K14, red), and CD248 (magenta) in a tissue section from donor C073 (scale bar = 100 µm). (right panel) Quantification of CD248 expression in different structures in tissue sections from donors with different BRCA1 mutational backgrounds, (AR duct n = 28, AR lobule n = 66, HR duct = 30, HR lobule = 52) Mann–Whitney U test (**** = < 0.0001, ns = > 0.05). E Graphical summary of CD105⁺ fibroblasts. CD105⁺ fibroblasts increase in proportion in older women and younger women with BRCA1 mutations. They have increased adipogenic potential and express a host of fibroblast and MSC markers. CD105⁺ fibroblasts are enriched for an immunosuppressive gene signature and secrete factors associated with ant-inflammatory macrophage polarization. CD105⁺ fibroblasts reduce the expression of TNFa in pro-inflammatory macrophages, and increase expression of CD163 and IL33 in anti-inflammatory macrophages while supporting the ability of anti-inflammatory macrophages to inhibit CD4⁺ T cell proliferation