Fig. 7: Cell-type-specific loss of TFAP4 predicts senescence phenotypes in human cell lines and PD patient tissue. | Nature Communications

Fig. 7: Cell-type-specific loss of TFAP4 predicts senescence phenotypes in human cell lines and PD patient tissue.

From: Systematic profiling reveals distinct senescence signatures and regulators across human brain cell types

Fig. 7: Cell-type-specific loss of TFAP4 predicts senescence phenotypes in human cell lines and PD patient tissue.

A Two-tailed Gene Set Enrichment Analysis of TFAP4 from inferred transcriptional network in BrdU-treated cells. Left—Activated (red) or inhibited (blue) target elements positions in ranked gene list based on log2FoldChange. Center—Normalized Enrichment Scores (NES) and associated p-values. Right—TFAP4 Transcripts per Million (TPM) values in DMSO (grey) and BrdU (red) treated cells. Positive and negative regulon targets separated by Pearson’s correlation. Statistical significance assessed using permutation testing (n = 1000) and p-values adjusted by Benjamini–Hochberg method. Data derived from RNA-seq analysis from Fig. 1 (n = 3 replicates). B Two-dimensional graphical visualizations based on PCA of TFAP4 transcriptional targets representing PC1 and PC2; top genetic contribution vectors overlayed from PC1. C Schematic depicting TFAP4 regulation of MIR22HG24, inducing senescence (Created in BioRender. Riessland, M. (2025) https://BioRender.com/xzt9mn0). D Normalized TFAP4 protein expression from Western blots (Fig. S6) in siSCR (grey) and TFAP4 KD (red) cells (n = 3 replicates). E Fold change TFAP4 RNA levels from quantitative PCRs (Fig. S7) in siSCR (grey) and TFAP4 KD (red) cells (n = 3 replicates). F Quantitative PCR of siSCR (grey) and siTFAP4 (red) treated cells of MIR22HG levels (n = 3 replicates). G Quantification of lamin B1 immunofluorescence staining in siSCR (grey) and siTFAP4 (red) treated cells (n = 9 replicates). H Quantification of nuclear area (µm2) based on lamin B1 staining in siSCR (grey) and siTFAP4 (red) treated cells (n = 9 replicates). I Quantification of γH2AX staining in siSCR (grey) and siTFAP4 (red) treated human cell lines (n = 9 replicates). J Quantification of Mitotracker Red CMXRos in siSCR (grey) and siTFAP4 (red) treated cells (n = 9 replicates). K Quantification of Lysotracker Deep Red in TFAP4 KD (red) and controls (grey) (n = 9 replicates). L Confocal images of age-matched control and PD patient human midbrain sections: TFAP4 (red), TH (white), and GFAP (green). Scale bars are 5 µm. Data analyzed by two-way ANOVA with Šídák’s multiple comparisons test. All graphs show mean with standard deviation (ns, p > 0.05, * p < 0.05, ** p < 0.01, *** p < 0.001). Source data and exact p-values are provided as a Source Data file.

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