IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39113-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39113-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39113-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Naveen Kumar & Pon Ganish Prakash & Christian Wentland & Shilpa Mary Kurian & Gaurav Jethva & Volker Brinkmann & Hans-Joachim Mollenkopf & Tobias Krammer & Christophe Toussaint & Antoine-Emmanuel Sali, 2024. "Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    3. Tim Flerlage & Jeremy Chase Crawford & E. Kaitlynn Allen & Danielle Severns & Shaoyuan Tan & Sherri Surman & Granger Ridout & Tanya Novak & Adrienne Randolph & Alina N. West & Paul G. Thomas, 2023. "Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Shirong Cao & Yu Pan & Andrew S. Terker & Juan Pablo Arroyo Ornelas & Yinqiu Wang & Jiaqi Tang & Aolei Niu & Sarah Abu Kar & Mengdi Jiang & Wentian Luo & Xinyu Dong & Xiaofeng Fan & Suwan Wang & Matth, 2023. "Epidermal growth factor receptor activation is essential for kidney fibrosis development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Christopher Bono & Yang Liu & Alexander Ferrena & Aneesa Valentine & Deyou Zheng & Bernice E. Morrow, 2023. "Single-cell transcriptomics uncovers a non-autonomous Tbx1-dependent genetic program controlling cardiac neural crest cell development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    9. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Ilmatar Rooda & Jasmin Hassan & Jie Hao & Magdalena Wagner & Elisabeth Moussaud-Lamodière & Kersti Jääger & Marjut Otala & Katri Knuus & Cecilia Lindskog & Kiriaki Papaikonomou & Sebastian Gidlöf & Ce, 2024. "In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    11. Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    12. Wei Yang & Li-Bo Liu & Feng-Liang Liu & Yan-Hua Wu & Zi-Da Zhen & Dong-Ying Fan & Zi-Yang Sheng & Zheng-Ran Song & Jia-Tong Chang & Yong-Tang Zheng & Jing An & Pei-Gang Wang, 2023. "Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Erick Armingol & Hratch M. Baghdassarian & Cameron Martino & Araceli Perez-Lopez & Caitlin Aamodt & Rob Knight & Nathan E. Lewis, 2022. "Context-aware deconvolution of cell–cell communication with Tensor-cell2cell," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Baptiste Lamarthée & Jasper Callemeyn & Yannick Van Herck & Asier Antoranz & Dany Anglicheau & Patrick Boada & Jan Ulrich Becker & Tim Debyser & Frederik De Smet & Katrien De Vusser & Maëva Eloudzeri , 2023. "Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    16. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    17. Tingting Liu & Zhenzhen Wang & Xiaotong Xue & Zhe Wang & Yuan Zhang & Zihao Mi & Qing Zhao & Lele Sun & Chuan Wang & Peidian Shi & Gongqi Yu & Meng Wang & Yonghu Sun & Fuzhong Xue & Hong Liu & Furen Z, 2024. "Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Jingtao Wang & Gregory J. Fonseca & Jun Ding, 2024. "scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    19. Inmaculada Ruz-Maldonado & John T. Gonzalez & Hanming Zhang & Jonathan Sun & Alicia Bort & Inamul Kabir & Richard G. Kibbey & Yajaira Suárez & Daniel M. Greif & Carlos Fernández-Hernando, 2024. "Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    20. Anjun Ma & Xiaoying Wang & Jingxian Li & Cankun Wang & Tong Xiao & Yuntao Liu & Hao Cheng & Juexin Wang & Yang Li & Yuzhou Chang & Jinpu Li & Duolin Wang & Yuexu Jiang & Li Su & Gang Xin & Shaopeng Gu, 2023. "Single-cell biological network inference using a heterogeneous graph transformer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39113-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.