Fig. 7: Expression of a phosphomimetic Ser 301 lamin A/C mutant induce CAF activation.

A Volcano plot showing differentially expressed genes in HDFs expressing a phosphomimetic Ser to Asp 301 mutant (S301D) versus wild-type lamin A (WT). Transcriptomic Analysis Console software (TAC), p values were calculated by two-tailed unpaired t-test. Genes with fold changes >1.5 and p values <0.05 are highlighted in red. A few upregulated genes are indicated. A complete list of differentially expressed genes is in Supplementary Data S4. B Genomic Distribution of Phospho-Ser301 Peaks overlapping with genes up or downregulated in S301D-overexpressing HDFs. C Functional classification of common genes upregulated in both shAR HDFs and S301D-overexpressing cells were classified using Panter bioinformatics software and curated manually. D Gene Set Enrichment Analysis (GSEA) of transcriptomic profiles of HDFs expressing the S301D mutant versus WT lamin A. Positive enrichment plots of the CAF matrisome gene signature (GSE71340). Black vertical bars indicate the position of each gene; the enrichment plot is shown in green with normalized enrichment score (NES) and FDR-q values. E Bar plot indicating additional CAF-related pathways enriched in S301D-expressing HDFs. F Distribution of gene signature of 200 upregulated genes in S301D expressing cells on fibroblasts derived from single-cell transcriptomic analysis of healthy skin, Bowen’s disease or cutaneous SCC (cSCC)⁵⁵. G The Uniform Manifold Approximation and Projection (UMAP) of fibroblasts clusters of Bowen’s disease and cutaneous SCC tumors⁵⁵ overlaid with the AddModule score of S301D signature (the top 200 upregulated genes in S301D expressing cells) and CAF signature⁹⁷. Each dot represents a single cell and color corresponds to the relative expression of the S301D signature within a cell. Blue corresponds to little/no gene expression, while red corresponds to increased gene expression as indicated in the scale. H Enrichment of the S301D lamin A/C gene signature on CAF and myofibroblast populations of head and neck squamous cell carcinoma (HNSCC) single cell clusters. Shown is the UMAP of different cell type clusters of HNSCC tumors⁵⁶ overlaid with the AddModule score of the top 200 upregulated genes in S301D expressing cells. Each dot represents a single cell and color corresponds to the relative expression of the S301D signature within a cell. Yellow corresponds to little/no gene expression, while red corresponds to increased gene expression as indicated in the scale. Source data for relevant graphs are in the Source Data file.