Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma
Name
nihms-1612044.pdf
Description
Accepted version
Size
2.85 MB
Format
Unknown
Checksum (MD5)
e1a80199d21a198ba87eed788360af7f
Author(s)
LaFave, Lindsay M.
Kartha, Vinay K.
Ma, Sai
Meli, Kevin
Del Priore, Isabella
Lareau, Caleb
Naranjo, Santiago
Westcott, Peter M.K.
Duarte, Fabiana M.
Sankar, Venkat
Date Issued
August 2020
Journal
Cancer Cell
Publisher
Elsevier BV
Version
Author's final manuscript
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.ccell.2020.06.006
