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 TGFβ-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 TGFβ-dependent alterations in gene expression when the Myc transgene is switched off. Our data show that Myc-induced target genes are downregulated in a TGFβ-independent manner. In contrast, TGFβ is required to upregulate a broad spectrum of genes that are characteristic for differenT-cell lineages when Myc is turned off. The analysis reveals a significant overlap between these Mycrepressed genes with genes that are targets of polycomb repressive complexes in embryonic stem cells. Therefore, TGFβdependent senescence is associated with gene expression patterns indicative of abortive cellular differentiation along several lineages.