Fig. 2: Transcriptomic analysis reveals elevated levels of BMP and WNT signaling pathways in ZMYND11 deficient NSCs, with BMP inhibition partially rescuing IPC production. | Nature Communications

Fig. 2: Transcriptomic analysis reveals elevated levels of BMP and WNT signaling pathways in ZMYND11 deficient NSCs, with BMP inhibition partially rescuing IPC production.

From: ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis

Fig. 2

a PCA of RNA-seq on hESCs and NSCs (hESCs, n = 2 replicates for WT and −/−, n = 2 clones for +/−; NSCs, n = 4 for +/+ and −/−, n = 8 for +/−). b Overlap of differentially expressed genes in ZMYND11-deficient NSCs (P value < 1e-100). c Gene ontology analysis on upregulated genes in ZMYND11-deficient NSCs. Gray dots: P.adjust > 0.1. d Western blot on p-SMAD1/5/8 and SMAD1 on NSCs (from left to right: WT + / + , HET2 + /−, HET4 + /-, KO1 −/−) with quantification (mean ± SEM, n = 3 for +/+ and −/−, n = 6 for +/−). e Neuron induction schematic and immunostaining for MAP2 (green), SOX2 (red) (n = 3). Scale bars, 10 μm. f Flow cytometry analysis for CD133 after neuron induction at d25 with quantification (mean ± SEM, n = 4 for +/+ and −/−, n = 8 for +/−). g High-dose BMP inhibition strategy (LDN193189: 500 nM) and immunostaining for MAP2 (green), TBR1 (red) after neuron induction (n = 3). Scale bars, 10 μm. h Flow cytometry analysis for TBR2 and FOXG1 on monolayer culture after standard differentiation vs. high-dose BMP inhibition at day 16 with quantification relative to WT in standard differentiation (mean ± SEM, n = 3 for +/+ and −/−, n = 5 for +/− for standard differentiation; n = 6 for +/+ and −/−, n = 11 for +/− for high-dose BMP inhibition). Statistics in (d, f): one-way ANOVA followed by Tukey’s test. Statistics in (b): hypergeometric test. Statistics in (c): over-representation analysis with P.adjust values by Benjamini-Hochberg method. Statistics in (h): one-way ANOVA followed by Sidak’s test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. P values in (d): +/− vs +/+, P = 0.0164; −/− vs +/+, P < 0.0001; −/− vs +/−, P = 0.0015. P values in (f): +/− vs +/+, P < 0.0001; −/− vs +/+, P = 0.0006; −/− vs +/−, P = 0.0018. P values in (h): for standard vs high BMPi, +/+ vs +/+, P = 0.9991; +/− vs +/−, P < 0.0001; −/− vs −/−, P = 0.0485; among high BMPi, +/− vs +/+, P < 0.0001; −/− vs +/+, P < 0.0001; −/− vs +/−, P = 0.0075. Source data are provided as a Source Data file.

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