Fig. 7: JUNB activates SASP induction in senescent MuSCs via enhancer regulation. | Nature Communications

Fig. 7: JUNB activates SASP induction in senescent MuSCs via enhancer regulation.

From: Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia

Fig. 7

A Heatmap showing snATAC-seq DORC regulation scores for top TF-SASP associations in human MuSCs. B, C Violin plot showing chromatin accessibility (B) and expression (C) of human (h)JUNB in young vs. aged MuSCs. p = 0.00032 (B), 0.038 (C). Wilcoxon tests, two-sided. D RT-qPCR detection of the hJUNB and SASP target expressions in young/aged MuSCs, n = 4. p = 0.0067 (JUNB), 0.044 (TGFB3), 0.033 (GDF15), 0.0018 (PLAUR), 0.039 (CXCL1), 0.011 (PDGFB). E RT-qPCR detection of the mouse (m)JunB and SASP target expressions in young (2 m)/aged(24 m) MuSCs, n = 3. p = 0.016 (JunB), 0.0087 (Tgfb3), 0.034 (Gdf15), 0.0048 (Cxcl1), 0.0044 (Pdgfb), 0.0029 (Csf3). F RT-qPCR detection of the mJunB and SASP targets expressions in Ctrl/JunB-iKO MuSCs, n = 5. p = 0.023 (Il1r1), 0.0072 (Plaur), 0.0017 (Cxcl1), 0.0020 (Pdgfb), 0.0055 (Csf3). G RT-qPCR detection of the mJunB and SASP target expressions in Ctrl/JunB-overexpressing MuSCs, n = 3. p = 0.037 (Il1r1), 0.041 (Plaur), 0.0012 (Cxcl1), 0.041 (Timp2). H Pie chart showing the distribution of snATAC-seq predicted hJUNB binding sites in young/aged human MuSCs. I Pie chart showing the distribution of mJunB binding in young/aged MuSCs, detected by CUT&RUN-seq. J Average H3K27ac signal profile ( ± 1 kb around mJunB sites). K, L Pie chart showing the overlapping of mJunB target genes (K) and SASP genes (L) (promoter and enhancer bound) in young/aged MuSCs. The young/aged unique SASP targets are listed. M Genomic snapshots on Cxcl1 locus showing the binding peaks of mJunB and H3K27ac in young/aged MuSCs. N, O Genomic coverage plot on CXCL1 locus showing the predicted hJUNB binding peaks in Sn vs. nSn (N) and young vs. aged (O) human MuSCs. P Chromatin openness level (DORC) versus normalized gene expression (SCT) dynamics of CXCL1 gene along MuSC aging pseudotime. Dotted line represents LOESS fit to the values obtained from sliding window bin averaged from DORC accessibility or SCT expression levels (n = 100 cells per bin). All the bar graphs are presented as mean + SD, two-sided paired Student’s t-test was used to calculate the statistical significance (B–G): *p <0.05, **p <0.01, ***p <0.001, n.s. = no significance. Source data are provided as a Source Data file.

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