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

• DOI: 10.1038/s41467-020-17492-y
• Publication Date: 2020-07-24T10:04:09Z
• Authors: Jiacheng Yao; Qionghua Cui; Wenyi Fan; Yuling Ma; Yamei Chen; Tianyuan Liu; Xiannian Zhang; Yiyi Xi; Chengcheng Wang; Linna Peng; Yingying Luo; Ai Lin; Wenjia Guo; Lin Lin; Yuan Lin; Wen Tan; Dongxin Lin; Chen Wu; Jianbin Wang
• Keywords: 0301 basic medicine; Esophageal Neoplasms; Science; T-Lymphocytes; Down-Regulation; Article; Mice; 03 medical and health sciences; Cell Line, Tumor; Tumor Microenvironment; Animals; Humans; Cell Proliferation; Q; Epithelial Cells; Fibroblasts; 3. Good health; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; Disease Models, Animal; Cell Transformation, Neoplastic; Female; Esophageal Squamous Cell Carcinoma; Single-Cell Analysis; Transcriptome; Transcription Factors

AbstractEsophageal 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.