Fig. 3: PU.1, C/EBPβ, and AP-1 TF cooperatively regulate aberrant lineage transition.

a Flow-cytometric analyses of CD115 and CD11b expression in biologically individual untreated (UT) vs. 5-day adriamycin (ADR)-exposed control;bcl2 lymphomas (n = 5 each), stably transduced with either a control (sh_ctrl) shRNA or shRNAs targeting Spi1 (sh_Spi1) or Cebpb (sh_Cebpb). Mean fluorescence intensities (MFI) relative to UT sh_ctrl are plotted. b Quantification of the respiratory burst capacity by NBT assay of control;bcl2 lymphomas, as in a (n = 4 each). a, b Bars indicate the mean fold-expression (a) or mean percentage of positive cells (b) ± SEM. P-values by two-sided ratio paired (comparisons indicated by connecting lines) or by two-sided one-sample t-test (comparing UT sh_TF to UT sh_ctrl). c Heatmap of qRT-PCR-based gene expression profiles comparing UT vs. 5-day ADR-exposed control;bcl2 lymphomas transduced with either control vector, cJunΔN, sh_Spi1, sh_Cebpb, or the combination of all three latter constructs (n = 3 individual lymphomas each). Analyzed transcripts encompass the directly disrupted TF and their target genes. d RNA-seq-based gene set enrichment analysis (GSEA) of individual therapy-induced senescent (TIS) lymphomas with Spi1 depletion (sh_Spi1) compared to sh_ctrl (n = 4 each), probing gene sets upregulated in macrophages (Mφ, top) and dendritic cells (DC, bottom). Negative normalized enrichment scores (NES) signify depletion in sh_Spi1 TIS. False discovery rate (FDR) as indicated. e Heatmap presentation of qRT-PCR-based gene expression data of PU.1 target transcripts in individual control;bcl2 lymphomas stably transduced with a 4-hydroxytamoxifen (4-OHT)-inducible PU.1-ER^T2 fusion construct, upon 6-day ADR exposure or left UT, and simultaneously exposed to 4-OHT or solvent control (n = 4). Source data are provided in the Source Data file.