{
  "id": 10726946,
  "title": "Epigenetic progression of pancreatic cancer to aggressive subtypes involves alternate routes of lineage reprogramming in subtype-intermediate progenitor cells",
  "url": "https://urgent.news/2026/09/29/epigenetic-progression-of-pancreatic-cancer-to-aggressive-subtypes",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-29T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754674v1?rss=1"
  },
  "original_language": "en",
  "account": "Pancreatic ductal adenocarcinoma (PDAC) arises from a complex plasticity of malignant cells, with epigenetic alterations playing a significant role. However, the underlying regulatory landscape remains poorly understood. To shed light on this, researchers analyzed 33 primary tumors and 7 metastases from 39 PDAC patients using single-cell ATAC-seq and RNA-seq profiles.\n\nThey identified a classical-basal subtype-intermediate progenitor state (SIP) characterized by co-accessibility of GATA6 and KRT17, which is associated with better clinical outcomes. Cells in this state show limited epigenetic reprogramming from premalignant epithelium and maintain gastric-intestinal differentiation, akin to neoplastic precursors. In contrast, lineages lacking this co-accessibility exhibit increased lineage and epithelial-mesenchymal plasticity.\n\nClassical PDACs that suppress basal gene accessibility activate neural-like progenitor (NRP) and tuft lineage enhancers, while basal committed tumors display evidence of esophageal transdifferentiation. Compared to SIP, classical-NRP and basal committed tumors have poorer prognoses and display distinct PD-1/PD-L1 immune proteomic phenotypes and myofibroblast epigenetic states, respectively.\n\nThe study highlights the intricate connections between lineage reprogramming, epithelial-mesenchymal transition (EMT), and epigenetic progression in human PDAC. These findings provide valuable insights into the progression of PDAC and may guide future therapeutic strategies targeting these specific lineages.",
  "summary": "Pancreatic ductal adenocarcinoma (PDAC) progression involves malignant cell state plasticity. Epigenetic changes underlie this plasticity, yet the PDAC cis-regulatory landscape remains understudied. To address this, we profiled 33 primary tumors and 7 metastases from 39 patients with single-cell ATAC-seq, paired with 10 single-cell RNA-seq profiles. We found that epigenetic GATA6+/KRT17+…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}