Fig. 4: p53 in MSCs contributes to response to murine Mdm2 inhibitor.

A Schematic view of the experimental design. B Direct fluorescence microscopy image of a longitudinal section of femur derived from a syngeneic Osx-Cre;Trp53^fl/fl AML mouse showing MSCs (green), leukemia cells (turquoise), normal hematopoietic cells (red) and DAPI (blue). The red box marks the region of interest shown in the right panel. C Kaplan-Meier survival curves of recipient mice reconstituted with p53-null AML1/ETO9a transformed leukemia cells. The treatment period is marked by the blue box. D Diagram showing the origin and isolation process of MSCs treated with MDM2 inhibitor or vehicle. GFP+ cells represent the population of MSCs and osteoprogenitors marked by Osx-cre, which were sorted for transcriptome analysis. E Mean-average plot of Log₂ mean expression versus Log2 fold change between treated and vehicle-treated MSCs. Red dots indicate genes with significantly higher expression in treated MSCs (Log₂FC > 1 and P < 0.05). Blue dots indicate genes with significantly lower expression in treated MSCs (Log₂FC < −1 and P < 0.05). F Heat map representing the transcriptome alteration in the indicated groups. log₂ expression values. n = 3. p < 0.01. G Top predicted annotations for pathways and functions ranked by Z-score by Ingenuity Pathway Analysis (IPA) for the top 20 differentially expressed genes. H IPA upstream regulator analysis on differentially expressed genes shown in F.