Extended Data Fig. 3: mTECs repress p53 upon maturation independently of AIRE.
From: Thymic epithelial cells amplify epigenetic noise to promote immune tolerance
a, Aggregate prevalence of p53-target motifs across accessible mTEC genomes (chromVAR deviation scores) overlayed on scATAC-seq UMAP from Fig. 1b. b,c, Mean chromVAR deviation scores of p53-target motifs (red) and mean fraction of scATAC-seq fragments within scATAC-seq peaks (WIP) (purple) (b) or mean aggregate expression of p53-target genes (green) (c) in mTECs across developmental axis. d, Representative flow cytometry plots of the frequencies of MDM2hi cells in singlets from thymic digest and indicated mature and immature mTEC compartments. e,f, Comparison of frequencies of MDM2lo and MDM2hi cells (e) or ratio of MDM2 mean fluorescence intensity (MFI) (f) between immature and mature mTECs. P-values for two-sided paired t-tests displayed. g–o, Expression levels of indicated genes overlayed on scATAC-seq UMAP from Fig. 1b. p, Rank-sorted differences in motif prevalence within accessible genomes (chromVAR deviation scores) of AIRE-deficient mTECs between indicated mTECs defined in Fig. 2e (and UMAP inset) for 884 known transcription factor motifs. q, Scatter plot comparing differential gene expression (transcripts per million=TPM) of 51 known regulators of p53 activity between AIRE-deficient mature and immature mTECs versus AIRE-sufficient mature and immature mTECs. Benjamini-Hochberg FDR for AIRE-deficient mature versus immature comparison indicated as point colors with highly significant differentially expressed genes (FDR ≤ 1e-9, fold-change ≥ 2 or ≤ 0.5) indicated as repressors (brown text) or promoters (green text) of p53 activity.
