Fig. 3 | Nature Communications

Fig. 3

From: Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion

Fig. 3The alternative text for this image may have been generated using AI.

DNA damage and activation of p53 and p53 target genes in Knl1 cKO brain. a Unique molecular identifier (UMI) RNA-seq volcano plot comparing cKO (n = 4) to ctrl (n = 7 animals) E15.5 cortex. P-value was calculated with likelihood ratio tests and false discovery rate (FDR) was calculated using the Benjamini–Hochberg procedure. Differentially expressed genes (FDR < 0.05) are indicated in red. b All 19 significantly upregulated genes. p53 target genes (pink), microglial genes (blue), and interneuronal genes (green) are indicated. c Droplet digital RT-PCR (ddRT-PCR) validated upregulation of p53 target genes Ano3, Eda2r, and Pvt1, and downregulation of Eomes in cKO compared to ctrl (mean, two-tailed unpaired t-test, ctrl: n = 7, cKO: n = 4 animals). d Immunostaining of E15.5 cortex revealed significant increases in the number of cells labeled by p53 or DNA damage marker γH2AX in cKO compared to ctrl (mean, two-tailed unpaired t-test, n = 3 animals, scale bar: 100 µm). p53 was localized to nuclei (solid arrowheads) and present in pyknotic cells (open arrowheads, inset scale bar: 5 µm). e Double immunostaining revealed p53 activation in SOX2+ NPCs in E15.5 cKO VZ (arrowheads). The vast majority of cells (89 ± 1.5%) with p53 activation were SOX2+ NPCs (mean, cKO: n = 4 animals). coloc. colocalization

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