Journal Article

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

Zhang, Xiannian, Fan, Wenyi, Cui, Qionghua, Liu, Tianyuan, Lin, Ai, Lin, Dongxin, Guo, Wenjia, Yao, Jiacheng, Luo, Yingying, Wang, Jianbin, Xi, Yiyi, Lin, Yuan, Lin, Lin, Chen, Yamei, Wu, Chen, Ma, Yuling, Tan, Wen, Peng, Linna, Wang, Chengcheng

2020

Overview

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. The multistep processes involved in the evolution of inflammation to invasive esophageal squamous cell carcinoma (ESCC) is unclear. Here, the authors report a mouse model of ESCC and the role of interplay between carcinogen-transformed epithelial cells and their microenvironment in ESCC development.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 631/67/1504/1477 / 631/67/327 / 64/60 / 82/51 / Animals / Blocking / Cancer / Carcinogens / CD8 antigen / Cell activation / Cell Line, Tumor / Cell Proliferation / Cell survival / Cell Transformation, Neoplastic - genetics / Cell Transformation, Neoplastic - metabolism / Disease Models, Animal / Down-Regulation / Epithelial cells / Epithelial Cells - pathology / Esophageal cancer / Esophageal Neoplasms - genetics / Esophageal Neoplasms - immunology / Esophageal Neoplasms - metabolism / Esophageal Neoplasms - pathology / Esophageal Squamous Cell Carcinoma / Esophagus / Evolution / Female / Fibroblasts - metabolism / Fibroblasts - pathology / Gene Expression Regulation, Neoplastic / Humanities and Social Sciences / Humans / Immune response / Inflammation / Invasiveness / Leukocytes (neutrophilic) / Macrophages / Mice / Mice, Inbred C57BL / Mimicry / multidisciplinary / Science / Science (multidisciplinary) / Single-Cell Analysis - methods / Squamous cell carcinoma / T-Lymphocytes / Transcription Factors / Transcriptome / Tumor Microenvironment