Fig. 5: Sox4 enhances epigenetic dysregulation observed after Tet2 KO in primary cells.

a Schematics representing the experimental workflow and analysis for generating Sox4- overexpressing primary HSPC in Tet2^fl/fl background. b Percentage of CD45.2 cells measured at different time points in the PB of mice transplanted with inducible Tet2 KO cells together with overexpression of GFP (Tet2 KO, n = 16) or Sox4 (Sox4 OE Tet2 KO, n = 13). Two-tailed unpaired t-test, Exact p-values are indicated on the figure. Data from 2 independent experiments are included. Line: Median. c Distribution of the indicated populations within Lin- cells in the BM of mice from b 3 weeks after transplant (Tet2 KO, n = 7; Sox4 OE Tet2 KO, n = 8). Data are presented as mean values +/- SEM. Mann-Whitney test; Exact p-values are indicated on the figure. Populations are defined as in⁷¹. d Plot showing the fold change in the accessibility of chromatin peaks comparing WT and Sox4 OE Tet2 KO GMP cells analyzed by scATAC-seq. Cells belonging to clusters 1,4,7,10,13 for GMP samples were included. Significantly (FDR < 0.01) upregulated peaks are colored in red while significantly downregulated peaks are colored in blue. e Plot showing the overlap between GMP chromatin signatures calculated in Fig. 1 and differential peaks in GMP comparing Tet2 KO vs WT (same as Fig. 2e) and Sox4 OE Tet2 KO vs WT. Level of significance is color coded. f Cumulative accessibility of differential upregulated (left) and downregulated (right) GMP peaks from Fig. 5d plotted on UMAP coordinates. g Plot showing relative distribution of WT and Sox4 OE Tet2 KO cells across the differentiation trajectory. Source data are provided as a Source Data file.