Transcriptional impact of Y Chromosome aneuploidy. (A) Illustration of the 47,XYY patient and control 46,XY fibroblasts and derived-iPSC clones used in the study. Three 47,XXY fibroblast lines have been reprogrammed to generate three independent 47,XYY iPSC clones for JS1 and four clones for JS2 and JS3. (HC) Healthy controls; (JS) Jacobs syndrome. The control 46,XY fibroblasts, and iPSCs have been described by Astro et al. (2022) and Astro and Adamo (2024). (B) PCA analysis of 46,XY (orange) and 47,XYY (blue) fibroblasts, iPSCs, and NCSs samples used in the study. (C) Schematic of human sex chromosomes listing the genes encoded from the X and Y Chromosome shared pseudoautosomal territories, PAR1 and PAR2, and from the divergent NPX and NPY regions. (D–F) Bar plots of the percentage of differential expressed genes (DEGs) over the total number of expressed genes in fibroblasts, iPSCs, and neural stem cells (NSCs). The specific number of DEGs and expressed genes are shown inside the bars for each chromosome. PAR DEGs are indicated in pink and assigned only to the X Chromosome. (MT) Mitochondrial genes. (G–I) Pie charts showing the number of autosomal and sex-chromosome DEGs in each cell type. The number of X- and Y-linked PAR, NPX, and NPY DEGs are indicated in the bars. Log2 fold change (Log2FC) > |0.58|, FDR < 0.05.
