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Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse

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Inflammation and Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2691))

Abstract

Identification of unique gene markers of normal and cancer stem cells is an effective strategy to study cells of origin and understand tumor behavior. Lineage tracing experiments using the Cre recombinase driven by a stem cell-specific promoter in the CreERT2 reporter mouse model enables identification of adult stem cells and delineation of stem cell activities in vivo. In our recent research on the mouse stomach, Iqgap3 was identified as a homeostatic stem cell marker located in the isthmus of the stomach epithelium. Lineage tracing with the Iqgap3-2A-CreERT2;Rosa26-LSL-tdTomato mouse model demonstrated stem cell activity in Iqgap3-expressing cells. Using the Iqgap3-2A-CreERT2 mouse model to target oncogenic KrasG12D expression to Iqgap3-expressing cells, we observed the rapid development of precancerous metaplasia in the stomach and proposed that aberrant Iqgap3-expressing cells may be critical determinants of early carcinogenesis. In this chapter, we detail a lineage tracing protocol to assess stem cell activity in the murine stomach. We also describe the procedure of inducing KrasG12D expression in Iqgap3-expressing homeostatic stem cells to explore their role as cells of origin and to trace the early cellular changes that precede neoplastic transformation.

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Acknowledgements

This work is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centre of Excellence initiative. The work is also supported by the Singapore Ministry of Health’s National Medical Research Council’s Open Fund Large Collaborative Grant (OFLCG18May-0023), the Singapore Ministry of Health’s National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-CIRG21jun-0003), and the National University of Singapore School of Medicine (NUSMed) Internal Grant Funding (NUHSRO/2019/086/StomachStemCell and NUHSRO/2022/043/NUSMed/25/LOA).

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Correspondence to Yoshiaki Ito .

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Matsuo, J., Chuang, L.S.H., Tong, J.J.L., Douchi, D., Ito, Y. (2023). Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse. In: Jenkins, B.J. (eds) Inflammation and Cancer. Methods in Molecular Biology, vol 2691. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3331-1_1

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  • DOI: https://doi.org/10.1007/978-1-0716-3331-1_1

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3330-4

  • Online ISBN: 978-1-0716-3331-1

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