Fig. 2: Transcriptome network analyses reveal that luminal mature cells orchestrate the matrisome landscape of basal and fibroblast cells.

a, Workflow for paired biopsy single-cell transcriptomics from six participants at baseline and 12 weeks after UA treatment. The workflow was created using BioRender (https://biorender.com). b, UMAP of breast tissue cells annotated by broad cell type. n = 115,875 cells. c, Dot plot of broad cell-type marker genes. The columns correspond to key markers (normalized per gene) with brackets detailing the cell type, and the rows correspond to the cell population identified in the dataset. d, Proportionality fold change (post-treatment to baseline) across broad cell types (left) and restricted to epithelial cells (right). Positive or negative changes denote enrichment or depletion post-treatment, respectively. Boxplot centre lines represent median values, box bounds indicate the 25th and 75th percentiles, and whiskers extend to the extreme datapoint within 1.5 times the interquartile range (IQR) of the boxplot hinges. Significance was calculated with a two-sided Student’s t-test adjusted P value for multiple comparisons using Benjamini–Hochberg correction. n = 6 tissue pairs. e, UpSet plot depicting downregulated genes (less than −0.25 logFC, P < 0.05, Memento analysis) post-treatment across broad cell types. The intersection size indicates the number of genes uniquely regulated within a single cell type or shared across multiple cell types. f, UpSet plot depicting downregulated genes that encode proteins that act as ligands (less than –0.25 logFC, P < 0.05, Memento analysis) post-treatment across broad cell types. g, CellChat analysis of incoming–outgoing interaction strength between broad cell types at baseline. The node size represents the number of interactions in each cell type. h,i, Differential L–R pathway signalling changes (post-treatment to baseline) across broad cell types (h) or within basal (BMYO1) and fibroblast (FB1–3) cell states (i). Negative values represent a decrease in L–R signalling post-treatment. j, Chord diagram of pairwise downregulated collagen gene signalling post-treatment (less than –0.25 logFC, P < 0.05) from basal and fibroblast cell states (sender cells) to all breast cell states (receiver cells with 5% or more receptor expression), highlighting the epithelial populations in light blue.