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

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 i...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458072/
https://www.ncbi.nlm.nih.gov/pubmed/33293280
http://dx.doi.org/10.1136/gutjnl-2020-322779
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author 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
author_facet 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
author_sort Matsuo, Junichi
collection PubMed
description 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.
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spelling pubmed-84580722021-10-07 Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair 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 Gut Stomach 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. BMJ Publishing Group 2021-10 2020-12-08 /pmc/articles/PMC8458072/ /pubmed/33293280 http://dx.doi.org/10.1136/gutjnl-2020-322779 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Stomach
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
Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
title Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
title_full Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
title_fullStr Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
title_full_unstemmed Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
title_short Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
title_sort iqgap3-ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair
topic Stomach
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458072/
https://www.ncbi.nlm.nih.gov/pubmed/33293280
http://dx.doi.org/10.1136/gutjnl-2020-322779
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