TGFbeta-dependent gene expression shows that senescence correlates with abortive differentiation along several lineages in Myc-induced lymphomas

Deregulated expression of Myc under the control of an immunoglobulin enhancer induces lymphoma formation in mice. The development of lymphomas is limited by TGF beta-dependent senescence and high levels of Myc expression are continuously required to antagonize senescence. The biological processes underlying senescence are not fully resolved. We report here a comprehensive analysis of TGF beta-dependent alterations in gene expression when the Myc transgene is switched off. Our data show that Myc-induced target genes are down-regulated in a TGF beta-independent manner. In contrast, TGF beta is required to upregulate a broad spectrum of genes that are characteristic for different T-cell lineages when Myc is turned off. The analysis reveals a significant overlap between these Myc-repressed genes with genes that are targets of polycomb repressive complexes in embryonic stem cells. Therefore, TGF beta-dependent senescence is associated with gene expression patterns indicative of abortive cellular differentiation along several lineages.