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The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis

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Abstract

The epithelial lining of the stomach undergoes rapid turnover to preserve its structural and functional integrity, a process driven by long-lived stem cells residing in the antral and corpus glands. Several subpopulations of gastric stem cells have been identified and their phenotypic and functional diversities linked to spatiotemporal specification of stem cells niches. Here, we review the biological features of gastric stem cells at various locations of the stomach under homeostatic conditions, as demonstrated by reporter mice, lineage tracing, and single cell sequencing. We also review the role of gastric stem cells in epithelial regeneration in response to injury. Moreover, we discuss emerging evidence demonstrating that accumulation of oncogenic drivers or alteration of stemness signaling pathways in gastric stem cells promotes gastric cancer. Given a fundamental role of the microenvironment, this review highlights the role reprogramming of niche components and signaling pathways under pathological conditions in dictating stem cell fate. Several outstanding issues are raised, such as the relevance of stem cell heterogeneity and plasticity, and epigenetic regulatory mechanisms, to Helicobacter pylori infection-initiated metaplasia-carcinogenesis cascades. With the development of spatiotemporal genomics, transcriptomics, and proteomics, as well as multiplexed screening and tracing approaches, we anticipate that more precise definition and characterization of gastric stem cells, and the crosstalk with their niche will be delineated in the near future. Rational exploitation and proper translation of these findings may bring forward novel modalities for epithelial rejuvenation and cancer therapeutics.

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Acknowledgements

We thank all the members in the laboratory for helpful discussions on the manuscript.

Funding

This work was supported by the National Key Research and Development Program of China (No. 2022YFA1105300 to Bin Wang), National Natural Science Foundation of China (NSFC Nos. 81822032, 91959111 and 81872027 to Bin Wang, 81902931 to Junyu Xiang), Natural Science Foundation of Chongqing (No. CSTC2019JCYJJQX0027 to Bin Wang, cstc2021jcyj-msxmX0340 to Qin Liu), Funding from the Jin Feng laboratory to Bin Wang, and Funding from the Army Medical University (Nos. 2019CXLCA001, 2018XLC2023, and 2019XQY19 to Bin Wang. 2019XQN16 to Qin Liu). Its contents represent the view(s) of the author(s) and do not necessarily represent the official views of the funding agencies.

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  1. Meng Liu, Qin Liu and Qiang Zou share co-first authorship.

Authors and Affiliations

  1. Department of Gastroenterology, Chongqing University Cancer Hospital, Chongqing University Medical School, Chongqing, 400030, P. R. China

    Meng Liu & Wei-Qing Chen

  2. Department of Gastroenterology & Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, P. R. China

    Meng Liu, Qin Liu, Qiang Zou, Jinyang Li, Zhaole Chu, Junyu Xiang & Bin Wang

  3. Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing University Medical School, Chongqing, 400030, P. R. China

    Qiang Zou

  4. Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, 110001, P. R. China

    Zhi-Feng Miao

  5. Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, P. R. China

    Bin Wang

  6. Jinfeng Laboratory, Chongqing, 401329, P. R. China

    Bin Wang

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Meng Liu wrote the manuscript draft, designed and drawn all the figures. Meng Liu, Qin Liu, and Qiang Zou collected all the reference and made the tables. Jinyang Li and Zhaole Chu provided technical assistance. Junyu Xiang, Wei-Qing Chen, Zhi-Feng Miao, Bin Wang discussed and amended the manuscript. Bin Wang, Wei-Qing Chen, and Zhi-Feng Miao supervised the whole process. Bin Wang and Zhi-Feng Miao edited the manuscript and approved the submission. All the authors contributed to the final version of the manuscript.

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Correspondence to Wei-Qing Chen, Zhi-Feng Miao or Bin Wang.

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Liu, M., Liu, Q., Zou, Q. et al. The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis. Cell Oncol. 46, 867–883 (2023). https://doi.org/10.1007/s13402-023-00802-z

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