Clims coordinate the expression of developmental gene signatures.

<p>(A–B) Heat map of (A) TEB (66 genes) and (B) duct (137 genes) DEGs in the DN-Clim mammary gland with CyberT p-value<0.01 in at least two time points. (C–D) Categories of enriched gene sets from the Molecular Signatures Database that significantly overlap with the (C) TEB and (D) duct DEG sets. Both gene sets are enriched with mammary stem cell and breast cancer genes. Vertical line represents p-value at 0.05. (E) Analysis of overall survival (OS) in UNC 337 cohort of patients classified into high and low expression groups based on median expression of the combined list of DEGs in the DN-Clim TEB and ducts demonstrates that high expression of Clim-regulated genes confers poor prognosis. HR: Hazard Ratio with 95% confidence interval. P-value derived from Log-rank test. (F) Fold change of Wnt-signaling factors in DN-Clim sorted basal cells suggests altered Wnt signaling. Fgfr2 is also downregulated. (G) Increased expression of epidermal differentiation genes in DN-Clim luminal cells suggests a role for basal cells in maintaining luminal cell fate. Luminal cell signaling factors ErbB2/3 and Fgfr2 are also downregulated.