Fig. 4: FoxO TF targets are key players in the naïve to formative pluripotency transition.
From: FoxO transcription factors actuate the formative pluripotency specific gene expression programme
a Boxplot illustrating expression of 2i-specific (n = 249, green), N24-specific (n = 889, blue), and 2i&N24 (n = 486, purple) FoxO1 targets in WT cells at N24, measured by RNA-seq. Data show log2FC relative to 2i and p values from Wilcoxon rank sum tests. Non-targets are shown in grey. b Bootstrapping analysis (30,000 draws) for gene-sets of the same size as the sample gene-sets (2i-specific, 249 genes; N24-specific, 889 genes; 2i&N24, 486 genes). The distribution of average log2FC is plotted, with p values indicating the probability of the predicted exceeding the measured effect-size. c Upset plot showing the overlap of FoxO1 targets with core naïve and formative markers. d Genome browser snapshots displaying FoxO1 ChIP-signal in WT on selected naïve markers in 2i (green) and N24 (blue). Called peaks are indicated (2i-only: green, N24-only: blue, shared: purple). e Genome browser snapshots showing FoxO1 ChIP-signal in WT cells on selected formative markers in 2i (green) and N24 (blue). Called peaks are indicated (2i-only: green, N24-only: blue, shared: purple). f Box plot depicting expression of formative genes (n = 832) in WT cells at N24, divided into FoxO1 N24 targets (blue) or non-targets (grey), as measured by RNA-seq. Data are shown as log2FC relative to 2i. p value from two-tailed Wilcoxon rank sum tests is indicated in the plot. g Box plot showing the expression of core formative genes (n = 12) in WT cells at N24, divided into FoxO1 N24 targets (blue) or non-targets (grey), measured by RNA-seq. Data are shown as log2FC relative to 2i. p value from two-tailed Wilcoxon rank sum test is indicated. h Box plot showing the expression of FoxO1 targets (n = 726, blue) and non-targets (n = 5061, grey) in E5.5 and E6.5 embryos28,68. Absolute log2FC relative to E4.5 are shown. p values from two-tailed Wilcoxon rank sum test are indicated. i Similar to (b), bootstrapping analysis (30,000 draws) for gene-sets of the same size as the sample gene-sets (n = group size). The distribution of average log2FC is plotted, with p values indicating the probability of the predicted exceeding the measured effect-size.
