Fig. 3.

Cell-type-specific sex signature. a Number of male (light blue) and female (pink) sexually differentially expressed genes (SDEGs) in each cell type (datasets A and B, paired t test pFDR < 0.2, female–male fold change >1.5). b Heatmap of relative expression levels of male and female SDEGs in MFs from datasets A and B. Genes are sorted by female–male fold change. Expression values are trimmed to range [−2, 2]. For genes with multiple names, only the first is shown and then period. c Heatmap of relative expression levels of 71 previously identified MF IFN-stimulated genes (MF-ISGs)³⁵ in datasets A and B. Gene symbols are indicated for MF-ISGs that are also SDEGs or known IFNα-response genes (according to MsigDB Hallmark gene sets). Expression values are trimmed to range [−1.5, 1.5]. In b, c, dotted horizontal white lines separate female from male upregulated genes. Dotted vertical white lines separate female and male samples. d Female–male fold change (log₂) distribution of MF-ISGs (71 genes, green) and all genes (1568 genes, excluding MF-ISGs, orange). The t test p value between distributions is 7.6 × 10⁻¹², with permutation p value <0.001. e Box plot presenting female–male log₂ fold change (FC) distribution of the genes in modules C1–C5 defined by Mostafavi et al.³⁵ from unstimulated macrophages. On each box, the central mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme data points not considered outliers, and the outliers are plotted individually in red. Modules whose distributions are significantly different from zero (one-sample two-sided t test pFDR < 0.05) are marked by asterisk. Source data for b–e are provided as a Source Data file