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

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 () and Jianbin Wang ()
Additional contact information
Jiacheng Yao: Tsinghua University
Qionghua Cui: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Wenyi Fan: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Yuling Ma: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Yamei Chen: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Tianyuan Liu: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Xiannian Zhang: Capital Medical University
Yiyi Xi: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Chengcheng Wang: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Linna Peng: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Yingying Luo: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Ai Lin: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Wenjia Guo: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Lin Lin: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Yuan Lin: Peking University
Wen Tan: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Dongxin Lin: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Chen Wu: Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Jianbin Wang: Tsinghua University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17492-y

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