RESEARCH ARTICLE

Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium

  • Ji Dong 1,2,8 ,
  • Xinglong Wu 3 ,
  • Xin Zhou 1,6 ,
  • Yuan Gao 1,7 ,
  • Changliang Wang 2 ,
  • Wendong Wang 1 ,
  • Weiya He 2,8 ,
  • Jingyun Li 1 ,
  • Wenjun Deng 2 ,
  • Jiayu Liao 2 ,
  • Xiaotian Wu 4 ,
  • Yongqu Lu 1 ,
  • Antony K. Chen 4 ,
  • Lu Wen 1,5 ,
  • Wei Fu , 1,6 ,
  • Fuchou Tang , 1,5,7
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  • 1. Biomedical Pioneering Innovation Center, Department of General Surgery, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China
  • 2. GMU-GIBH Joint School of Life Sciences, Guangzhou Laboratory, Guangzhou Medical University, Guangzhou 510799, China
  • 3. College of Animal Science and Technology, Hebei Agricultural University, Baoding 071001, China
  • 4. Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
  • 5. Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China
  • 6. Peking University Third Hospital Cancer Center, Beijing 100191, China
  • 7. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
  • 8. Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510320, China
fuwei@bjmu.edu.cn
tangfuchou@pku.edu.cn

Received date: 03 Sep 2021

Accepted date: 30 Oct 2022

Published date: 15 Jun 2023

Copyright

2022 The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.

Abstract

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.

Cite this article

Ji Dong , Xinglong Wu , Xin Zhou , Yuan Gao , Changliang Wang , Wendong Wang , Weiya He , Jingyun Li , Wenjun Deng , Jiayu Liao , Xiaotian Wu , Yongqu Lu , Antony K. Chen , Lu Wen , Wei Fu , Fuchou Tang . Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium[J]. Protein & Cell, 2023 , 14(6) : 433 -447 . DOI: 10.1093/procel/pwac059

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