Single-cell transcriptomic analysis in a mouse model deciphers cell transition states in the multistep development of esophageal cancer

Nat Commun. 2020 Jul 24;11(1):3715. doi: 10.1038/s41467-020-17492-y.

Abstract

Esophageal squamous cell carcinoma (ESCC) is prevalent in some geographical regions of the world. ESCC development presents a multistep pathogenic process from inflammation to invasive cancer; however, what is critical in these processes and how they evolve is largely unknown, obstructing early diagnosis and effective treatment. Here, we create a mouse model mimicking human ESCC development and construct a single-cell ESCC developmental atlas. We identify a set of key transitional signatures associated with oncogenic evolution of epithelial cells and depict the landmark dynamic tumorigenic trajectories. An early downregulation of CD8+ response against the initial tissue damage accompanied by the transition of immune response from type 1 to type 3 results in accumulation and activation of macrophages and neutrophils, which may create a chronic inflammatory environment that promotes carcinogen-transformed epithelial cell survival and proliferation. These findings shed light on how ESCC is initiated and developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Epithelial Cells / pathology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Single-Cell Analysis / methods*
  • T-Lymphocytes
  • Transcription Factors
  • Transcriptome*
  • Tumor Microenvironment

Substances

  • Transcription Factors