Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma

Lindsay M. LaFave, Vinay K. Kartha, Sai Ma, Kevin Meli, Isabella Del Priore, Caleb Lareau, Santiago Naranjo, Peter M.K. Westcott, Fabiana M. Duarte, Venkat Sankar, Zachary Chiang, Alison Brack, Travis Law, Haley Hauck, Annalisa Okimoto, Aviv Regev, Jason D. Buenrostro, Tyler Jacks

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Regulatory networks that maintain functional, differentiated cell states are often dysregulated in tumor development. Here, we use single-cell epigenomics to profile chromatin state transitions in a mouse model of lung adenocarcinoma (LUAD). We identify an epigenomic continuum representing loss of cellular identity and progression toward a metastatic state. We define co-accessible regulatory programs and infer key activating and repressive chromatin regulators of these cell states. Among these co-accessibility programs, we identify a pre-metastatic transition, characterized by activation of RUNX transcription factors, which mediates extracellular matrix remodeling to promote metastasis and is predictive of survival across human LUAD patients. Together, these results demonstrate the power of single-cell epigenomics to identify regulatory programs to uncover mechanisms and key biomarkers of tumor progression.

Original languageEnglish (US)
Pages (from-to)212-228.e13
JournalCancer Cell
Volume38
Issue number2
DOIs
StatePublished - Aug 10 2020
Externally publishedYes

Keywords

  • cancer
  • epigenomics
  • epithelial-to-mesenchymal transition
  • metastasis
  • non-small cell lung cancer
  • single cell

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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