Extended Data Fig. 3: Progenitor-like tumour cells in male PFA-EPNs upregulate transcriptional regulatory networks retained from early embryonic development and are associated with worse survival outcomes.
From: Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma
a, Sex-biased regulons in GP-like tumours. Regulon activity was computed independently in male and female PFA cells and subsequently integrated based on shared regulons for visualization. Male-biased regulons are shown in blue, the top 20 female-biased regulons are shown in red, and regulons with comparable activity between sexes that are relevant to GPs are highlighted in black. b, Genes and regulatory network master regulators identified by single-cell differential expression and regulatory network analysis showing significant male-biased pseudobulk expression per sample. Female (n = 8) and male (n = 18). In box plots, the centre line denotes the median, box hinges indicate the 25th and 75th percentiles, and whiskers mark 1.5× the IQR. P values were calculated using a two-sided Student’s t-test. *P < 0.05, **P < 0.01, ***P < 0.001. Exact P values are provided in the Source Data. c, Dot plot visualization of male-biased gene expression in the GP-like tumour cluster by sex. F, female; M, male. d, UMAP visualization of average expression of the male-biased GP-like tumour gene signature in PFA tumours from females versus males. e, Top 5 pathways enriched in the male-biased GP-like tumour gene signature. Enrichment was assessed using a one-sided cumulative hypergeometric test with g:SCS multiple-testing correction. Terms with adjusted P < 0.05 were considered significant. f, Dot plot visualization of male-biased regulatory networks (SCENIC) in the GP-like tumour cluster by sex. F, female; M, male. g, UMAP visualization of average expression of the male-biased GP-like tumour TF signature in tumours from females versus males. h,i, Correlation of male-biased gene (h) and TF (i) signature expression in the GP-like cluster with tumour cell-type fractions in male patients with PFA-EPN from scRNA-seq cohort (n = 18). j,k, Kaplan–Meier curves of OS (j) and PFS (k) in male patients with PFA-EPN (n = 39), stratified by expression of the GP-like tumour male-biased gene signature in a microarray cohort treated with standard therapy (complete tumour resection and radiation). Statistical analyses were performed using two-sided log-rank test, shaded areas indicate 95% confidence intervals.
