TGFβ-dependent gene expression shows that senescence correlates with abortive differentiation along several lineages

Judith Müller1, Birgit Samans, Jan van Riggelen

  • 1Theodor Boveri Institute, Biocenter, University of Würzburg, Würzburg, Germany.

Insights

Turning off Myc expression in lymphoma-prone mice triggers TGFβ-dependent cellular differentiation, revealing insights into senescence and T-cell lineage development.

Area of Science:

  • * Molecular biology
  • * Cancer research
  • * Immunology

Background:

  • * Deregulated Myc expression drives lymphoma in mice.
  • * Transforming growth factor beta (TGFβ)-dependent senescence limits lymphoma development.
  • * Continuous high Myc levels are needed to counteract senescence.

Purpose of the Study:

  • * To comprehensively analyze TGFβ-dependent gene expression changes after Myc transgene inactivation.
  • * To elucidate the biological processes underlying TGFβ-dependent senescence.

Main Methods:

  • * Gene expression profiling in mice with inducible Myc transgenes.
  • * Analysis of TGFβ-dependent and -independent gene regulation.
  • * Comparison of gene expression patterns with Polycomb repressive complex targets.

Main Results:

  • * Myc-induced genes decrease independently of TGFβ upon Myc inactivation.
  • * TGFβ upregulates T-cell lineage-specific genes when Myc is off.
  • * Myc-repressed genes show overlap with Polycomb targets in stem cells.

Conclusions:

  • * TGFβ-dependent senescence involves gene expression patterns of abortive cellular differentiation.
  • * Myc inactivation leads to TGFβ-mediated upregulation of lineage-specific genes.
  • * Findings link senescence, differentiation, and Polycomb regulation in lymphoma.

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