Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair

Junichi Matsuo, Daisuke Douchi, Khine Myint, Naing Naing Mon, Akihiro Yamamura, Kazuyoshi Kohu, Dede Liana Heng, Sabirah Chen, Nur Astiana Mawan, Napat Nuttonmanit, Ying Li, Supriya Srivastava, Shamaine Wei Ting Ho, Nicole Yee Shin Lee, Hong Kai Lee, Makoto Adachi, Atsushi Tamura, Jinmiao Chen, Henry Yang, Ming TehJimmy Bok Yan So, Wei Peng Yong, Patrick Tan, Khay Guan Yeoh, Linda Shyue Huey Chuang, Sachiko Tsukita, Yoshiaki Ito

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Tissue stem cells are central regulators of organ homoeostasis. We looked for a protein that is exclusively expressed and functionally involved in stem cell activity in rapidly proliferating isthmus stem cells in the stomach corpus. Design: We uncovered the specific expression of Iqgap3 in proliferating isthmus stem cells through immunofluorescence and in situ hybridisation. We performed lineage tracing and transcriptomic analysis of Iqgap3 +isthmus stem cells with the Iqgap3-2A-tdTomato mouse model. Depletion of Iqgap3 revealed its functional importance in maintenance and proliferation of stem cells. We further studied Iqgap3 expression and the associated gene expression changes during tissue repair after tamoxifen-induced damage. Immunohistochemistry revealed elevated expression of Iqgap3 in proliferating regions of gastric tumours from patient samples. Results: Iqgap3 is a highly specific marker of proliferating isthmus stem cells during homoeostasis. Iqgap3+isthmus stem cells give rise to major cell types of the corpus unit. Iqgap3 expression is essential for the maintenance of stem potential. The Ras pathway is a critical partner of Iqgap3 in promoting strong proliferation in isthmus stem cells. The robust induction of Iqgap3 expression following tissue damage indicates an active role for Iqgap3 in tissue regeneration. Conclusion: IQGAP3 is a major regulator of stomach epithelial tissue homoeostasis and repair. The upregulation of IQGAP3 in gastric cancer suggests that IQGAP3 plays an important role in cancer cell proliferation.

Original languageEnglish
Article number2020322779
JournalGut
DOIs
Publication statusAccepted/In press - 2020
Externally publishedYes

Keywords

  • cell proliferation
  • gastric cancer
  • gastric pre-cancer
  • gastric wound repair
  • stem cells

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair'. Together they form a unique fingerprint.

Cite this