Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
| Autor: | Khine Myint, Kazuyoshi Kohu, Jinmiao Chen, Dede Liana Heng, Makoto Adachi, Sachiko Tsukita, Napat Nuttonmanit, Nur Astiana Mawan, Nicole Yee Shin Lee, Ying Li, Shamaine Wei Ting Ho, Junichi Matsuo, Khay Guan Yeoh, Sabirah Chen, Henry Yang, Atsushi Tamura, Wei Peng Yong, Naing Naing Mon, Hong Kai Lee, Jimmy Bok Yan So, Supriya Srivastava, Daisuke Douchi, Akihiro Yamamura, Patrick Tan, Linda Shyue Huey Chuang, Yoshiaki Ito, Ming Teh |
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| Rok vydání: | 2020 |
| Předmět: |
Cell type
Mice Inbred Strains Biology Transcriptome Mice Downregulation and upregulation Stomach Neoplasms Gene expression Biomarkers Tumor Animals Homeostasis Cell growth Gene Expression Profiling Stem Cells gastric cancer GTPase-Activating Proteins Stomach Gastroenterology gastric pre-cancer Cell biology Mice Inbred C57BL Disease Models Animal Tamoxifen cell proliferation gastric wound repair Gastric Mucosa Immunohistochemistry Stem cell |
| Zdroj: | Gut |
| ISSN: | 1468-3288 |
| Popis: | ObjectiveTissue 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.DesignWe 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.ResultsIqgap3 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.ConclusionIQGAP3 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. |
| Databáze: | OpenAIRE |
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