Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis

The response to tumor-initiating inflammatory and genetic insults can vary among morphologically indistinguishable cells, suggesting as yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins and impact of such plasticity, we performed single-cell analyses on normal, inflamed, premalignant, and malignant tissues in autochthonous models of pancreatic cancer. We reproducibly identified heterogeneous cell states that are primed for diverse, late-emerging neoplastic fates and linked these to chromatin remodeling at cell-cell communication loci. Using an inference approach, we revealed signaling gene modules and tissue-level cross-talk, including a neoplasia-driving…

• DR
  Damon Runyon Cancer Research Foundation
• MS
  Memorial Sloan-Kettering Cancer Center

  Award: CA008748
• MU
  McGill University
• DK
  Deutsches Krebsforschungszentrum
• MD
  Ministerio de Ciencia e Innovación

  Award: PID2021-128102OA-I00
• NI
  National Institutes of Health

  Award: R25 CA233208
• NC
  National Cancer Institute

  Awards: R25 CA233208, CA008748, CA209975