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Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma.
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; Chiang, Zachary; Brack, Alison; Law, Travis; Hauck, Haley; Okimoto, Annalisa; Regev, Aviv; Buenrostro, Jason D; Jacks, Tyler.
Afiliação
  • LaFave LM; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138,
  • Kartha VK; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Ma S; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Meli K; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Del Priore I; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Lareau C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Naranjo S; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Westcott PMK; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Duarte FM; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Sankar V; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Chiang Z; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Brack A; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Law T; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hauck H; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Okimoto A; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Regev A; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Buenrostro JD; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: jason_buenrostro@harvard.edu.
  • Jacks T; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 0214
Cancer Cell ; 38(2): 212-228.e13, 2020 08 10.
Article em En | MEDLINE | ID: mdl-32707078
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Regulação Neoplásica da Expressão Gênica / Modelos Animais de Doenças / Epigenômica / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Regulação Neoplásica da Expressão Gênica / Modelos Animais de Doenças / Epigenômica / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article