Figure 7 from FOXR2 Targets LHX6⁺/DLX⁺ Neural Lineages to Drive Central Nervous System Neuroblastoma

Foxr2 chromatin binding sites in Foxr2 p53^LOF neurosphere show enrichment in ETS and glial pathways. A, Validation of FOXR2 overexpression and p53 downregulation in ex vivoFoxr2 p53^LOF neurospheres by qRT-PCR. B, Validation of Nkx2-1, Lhx6, Dlx5, Dlx6, Emx2, Sox10, Olig1, Olig2, and Pdgfra expression in Foxr2 p53^LOF neurospheres by qRT-PCR. Foxr2 p53^LOF cell lines are positive for MGE markers and mirror the transcriptomic profile observed in patients. C, Kaplan–Meier curves depicting survival following orthotopic (striatal) injection of 150,000 Foxr2 p53^LOF cells (n = 5). D, Intersection of Foxr2 CUT&RUN peaks (n = 2 replicates) with ATAC peaks from single-cell multiome profiling of the murine Foxr2 p53^LOF model, used for filtering peaks. E, Top enriched TF motifs in filtered Foxr2 CUT&RUN peaks by adjusted P value. For visualization, the figure includes the top 13 motifs, colored and grouped by TF types. F, Tracks at Gad1 and Dlx5 genomic regions showing Foxr2 CUT&RUN and bulk RNA-seq in Foxr2 p53^LOF murine cell lines and pseudobulk ATAC tracks of malignant cells by cell type from single-cell multiome profiling of Foxr2 p53^LOF mouse model tissue. G, Tracks as in F at genomic regions for Hand2 and Ets1. H, Tracks as in F at genomic regions for Sox family glial TFs. I, Tracks as in F at genomic regions for key oligodendrocyte lineage genes. Adj, adjusted; Astro, astrocytes; INH, inhibitory neurons; LRL, lower rhombic lip; OL, oligodendrocytes.