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Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis

Author

Listed:
  • Hitomi Takada

    (Graduate School of Science and Technology, Nara Institute of Science and Technology)

  • Yohei Sasagawa

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research
    Tokyo Medical and Dental University)

  • Mika Yoshimura

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research)

  • Kaori Tanaka

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research)

  • Yoshimi Iwayama

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research
    Tokyo Medical and Dental University)

  • Tetsutaro Hayashi

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research)

  • Ayako Isomura-Matoba

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research)

  • Itoshi Nikaido

    (Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research
    Tokyo Medical and Dental University
    University of Tsukuba)

  • Akira Kurisaki

    (Graduate School of Science and Technology, Nara Institute of Science and Technology)

Abstract

Defects in gastric progenitor cell differentiation are associated with various gastric disorders, including atrophic gastritis, intestinal metaplasia, and gastric cancer. However, the mechanisms underlying the multilineage differentiation of gastric progenitor cells during healthy homeostasis remain poorly understood. Here, using a single-cell RNA sequencing method, Quartz-Seq2, we analyzed the gene expression dynamics of progenitor cell differentiation toward pit cell, neck cell, and parietal cell lineages in healthy adult mouse corpus tissues. Enrichment analysis of pseudotime-dependent genes and a gastric organoid assay revealed that EGFR-ERK signaling promotes pit cell differentiation, whereas NF-κB signaling maintains gastric progenitor cells in an undifferentiated state. In addition, pharmacological inhibition of EGFR in vivo resulted in a decreased number of pit cells. Although activation of EGFR signaling in gastric progenitor cells has been suggested as one of the major inducers of gastric cancers, our findings unexpectedly identified that EGFR signaling exerts a differentiation-promoting function, not a mitogenic function, in normal gastric homeostasis.

Suggested Citation

  • Hitomi Takada & Yohei Sasagawa & Mika Yoshimura & Kaori Tanaka & Yoshimi Iwayama & Tetsutaro Hayashi & Ayako Isomura-Matoba & Itoshi Nikaido & Akira Kurisaki, 2023. "Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39113-0
    DOI: 10.1038/s41467-023-39113-0
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    References listed on IDEAS

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    1. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. Ji-Eun Kim & Lijiang Fei & Wen-Chi Yin & Sabrina Coquenlorge & Abilasha Rao-Bhatia & Xiaoyun Zhang & Sammy Shun Wai Shi & Ju Hee Lee & Noah A. Hahn & Wasi Rizvi & Kyoung-Han Kim & Hoon-Ki Sung & Chi-c, 2020. "Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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    1. Elisa Manieri & Guodong Tie & Ermanno Malagola & Davide Seruggia & Shariq Madha & Adrianna Maglieri & Kun Huang & Yuko Fujiwara & Kevin Zhang & Stuart H. Orkin & Timothy C. Wang & Ruiyang He & Neil Mc, 2023. "Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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