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.
journal_name
Gutjournal_title
Gutauthors
Matsuo J,Douchi D,Myint K,Mon NN,Yamamura A,Kohu K,Heng DL,Chen S,Mawan NA,Nuttonmanit N,Li Y,Srivastava S,Ho SWT,Lee NYS,Lee HK,Adachi M,Tamura A,Chen J,Yang H,Teh M,So JB,Yong WP,Tan P,Yeoh KG,Chuang LSHdoi
10.1136/gutjnl-2020-322779subject
Has Abstractpub_date
2020-12-08 00:00:00eissn
0017-5749issn
1468-3288pii
gutjnl-2020-322779pub_type
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