Fig 2: The YAP1-MAMLD1 exerts its oncogenicity via TEAD-mediated transcriptional control. a Western blot of human CTGF and CYR61 in LN229 cells transiently transfected with indicated genes. The transgene protein products were tagged by HA. b Western blot of pan-TEAD proteins (pan-TEADs) after immunoprecipitation with an anti-HA antibody for HA-tagged YAP1-MAMLD1 fusion protein, confirming that the S94A-mutated YAP1-MAMLD1 fusion has lost the ability to bind TEAD transcription factors. c Western blot of YAP1-Tead targets CTGF and CYR61 using NIH/3T3 cells transfected with indicated genes. The transgene protein products were tagged by HA. d, e Luciferase-based d in vivo bioluminescence images at weeks 1–3 after birth and e Kaplan–Meier curves of animals electroporated with S94A-mutated YAP1-MAMLD1 fusion. Cyan curve is same as in Fig. 3k

Fig 3: Overlap of TRIAD and senescence phenotypes in neurons of AD model mice.a Triple staining of the cerebral cortex of AD model mice was performed at 8 months of age. A Lamin B1 ring-negative and nuclear YAP-negative cell (TRIAD-senescence overlapped phenotype) was observed at the center of pSer46-MARCKS stains (thick white arrow). Around the pSer46-MARCKS foci, many Lamin B1 ring-negative and nuclear YAP-negative cells are observed, showing overlap of TRIAD and senescence phenotypes (thin white arrow). Nuclear YAP-positive cells kept Lamin B1 ring (green arrow). The right lower table shows a positive relationship between TRIAD and senescence, and the statistic confirmation by Fisher’s exact test. b Intravenous administration of human monoclonal anti-HMGB1 antibody (#129) reduced the number of senescent cells both in the cerebral cortex of 5xFAD and APP-KI mice.

Fig 4: (A) MLT regulated the expression of Col2a through the MT1 binding mediated transcription of YAP1 in antler mesenchymal cells. (B) MLT effectively inhibited VEGF-induced degeneration of antler chondrocytes through inhibition of p-STAT5/IL-6 and activation of p-AKT/p-CREB dependent on Sox9 expression.

Fig 5: YAP1-MAMLD1-driven mouse tumors mimic molecular characteristics of ST-EPN-YAP1s. a IHC of E15.5 cortical plate of wildtype animals with Pax6/Ki67 (left) and Pax6/Eomes (right). MZ marginal zone, CP cortical plate, IZ intermediate zone, SVZ subventricular zone, VZ ventricular zone. Scale bar, 50 µm. b and c Box plots of transcriptome levels of b PAX6 and c EOMES across human EPN subgroups and pediatric glioblastoma multiforme (pGBMs). The center line, box limits, whiskers, and points indicate the median, upper/lower quartiles, 1.5× interquartile range and outliers, respectively. d–s IHC of brains electroporated with YAP1-MAMLD1-IRES-GFP at E13.5 at d–g E15.5, h–k P0, l–o P7 and p–s adult stages with anti-Ki67, anti-Pax6, and anti-Eomes antibodies. The margin of the ventricular zone shown in dotted lines. Scale bar in (e), 100 µm (for d, e), the bar in (q), 200 µm (for h, i, l, m, p, and q) and the bar in s, 50 µm (for f, g, j, k, n, o, r, and s). t, u (t) Principal component analysis and (u) hierarchical clustering based on orthologous gene expression data from human ST-EPN-RELA (red) and ST-EPN-YAP1 (cyan) tumors and YAP1-MAMLD1 fusion-driven mouse tumors (blue). Each dot represents one tumor