Please use this identifier to cite or link to this item: https://doi.org/10.1136/gutjnl-2020-322779
Title: Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
Authors: Matsuo, Junichi
Douchi, Daisuke
Myint, Khine
Mon, Naing Naing 
Yamamura, Akihiro 
Kohu, Kazuyoshi
Heng, Dede Liana
Chen, Sabirah 
Mawan, Nur Astiana 
Nuttonmanit, Napat 
Li, Ying 
Srivastava, Supriya 
Ho, Shamaine Wei Ting 
Lee, Nicole Yee Shin
Lee, Hong Kai
Adachi, Makoto
Tamura, Atsushi
Chen, Jinmiao 
Yang, Henry 
Teh, Ming 
So, Jimmy Bok-Yan 
Yong, Wei Peng
Tan, Patrick 
Yeoh, Khay Guan 
Chuang, Linda Shyue Huey
Tsukita, Sachiko
Ito, Yoshiaki
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
GASTRIC CHIEF CELLS
PROGENITOR-CELL
EXPRESSION
METAPLASIA
MOUSE
EPITHELIUM
CANCER
IDENTIFICATION
REGENERATION
SURVIVAL
Issue Date: 1-Oct-2021
Publisher: BMJ PUBLISHING GROUP
Citation: Matsuo, Junichi, Douchi, Daisuke, Myint, Khine, Mon, Naing Naing, Yamamura, Akihiro, Kohu, Kazuyoshi, Heng, Dede Liana, Chen, Sabirah, Mawan, Nur Astiana, Nuttonmanit, Napat, Li, Ying, Srivastava, Supriya, Ho, Shamaine Wei Ting, Lee, Nicole Yee Shin, Lee, Hong Kai, Adachi, Makoto, Tamura, Atsushi, Chen, Jinmiao, Yang, Henry, Teh, Ming, So, Jimmy Bok-Yan, Yong, Wei Peng, Tan, Patrick, Yeoh, Khay Guan, Chuang, Linda Shyue Huey, Tsukita, Sachiko, Ito, Yoshiaki (2021-10-01). Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair. GUT 70 (10) : 1833-1846. ScholarBank@NUS Repository. https://doi.org/10.1136/gutjnl-2020-322779
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.
Source Title: GUT
URI: https://scholarbank.nus.edu.sg/handle/10635/206146
ISSN: 00175749
14683288
DOI: 10.1136/gutjnl-2020-322779
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