Literature DB >> 28581476

Lgr5-expressing chief cells drive epithelial regeneration and cancer in the oxyntic stomach.

Marc Leushacke1, Si Hui Tan1, Angeline Wong1, Yada Swathi1, Amin Hajamohideen1, Liang Thing Tan1, Jasmine Goh1, Esther Wong1, Simon L I J Denil1, Kazuhiro Murakami2, Nick Barker1,2,3.   

Abstract

The daily renewal of the corpus epithelium is fuelled by adult stem cells residing within tubular glands, but the identity of these stem cells remains controversial. Lgr5 marks homeostatic stem cells and 'reserve' stem cells in multiple tissues. Here, we report Lgr5 expression in a subpopulation of chief cells in mouse and human corpus glands. Using a non-variegated Lgr5-2A-CreERT2 mouse model, we show by lineage tracing that Lgr5-expressing chief cells do not behave as corpus stem cells during homeostasis, but are recruited to function as stem cells to effect epithelial renewal following injury by activating Wnt signalling. Ablation of Lgr5+ cells severely impairs epithelial homeostasis in the corpus, indicating an essential role for these Lgr5+ cells in maintaining the homeostatic stem cell pool. We additionally define Lgr5+ chief cells as a major cell-of-origin of gastric cancer. These findings reveal clinically relevant insights into homeostasis, repair and cancer in the corpus.

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Year:  2017        PMID: 28581476     DOI: 10.1038/ncb3541

Source DB:  PubMed          Journal:  Nat Cell Biol        ISSN: 1465-7392            Impact factor:   28.824


  41 in total

1.  Somatic activation of the K-ras oncogene causes early onset lung cancer in mice.

Authors:  L Johnson; K Mercer; D Greenbaum; R T Bronson; D Crowley; D A Tuveson; T Jacks
Journal:  Nature       Date:  2001-04-26       Impact factor: 49.962

2.  Lgr5 marks cycling, yet long-lived, hair follicle stem cells.

Authors:  Viljar Jaks; Nick Barker; Maria Kasper; Johan H van Es; Hugo J Snippert; Hans Clevers; Rune Toftgård
Journal:  Nat Genet       Date:  2008-10-12       Impact factor: 38.330

3.  The Intestinal Wnt/TCF Signature.

Authors:  Laurens G Van der Flier; Jacob Sabates-Bellver; Irma Oving; Andrea Haegebarth; Mariagrazia De Palo; Marcello Anti; Marielle E Van Gijn; Saskia Suijkerbuijk; Marc Van de Wetering; Giancarlo Marra; Hans Clevers
Journal:  Gastroenterology       Date:  2006-08-18       Impact factor: 22.682

4.  beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer.

Authors:  T Brabletz; A Jung; S Dag; F Hlubek; T Kirchner
Journal:  Am J Pathol       Date:  1999-10       Impact factor: 4.307

5.  Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice.

Authors:  Sachiyo Nomura; Hirokazu Yamaguchi; Masako Ogawa; Timothy C Wang; Jeffrey R Lee; James R Goldenring
Journal:  Am J Physiol Gastrointest Liver Physiol       Date:  2005-02       Impact factor: 4.052

6.  Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa.

Authors:  Howard C Crawford; Uma S Krishna; Dawn A Israel; Lynn M Matrisian; M Kay Washington; Richard M Peek
Journal:  Gastroenterology       Date:  2003-10       Impact factor: 22.682

7.  Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas.

Authors:  S McDonnell; M Navre; R J Coffey; L M Matrisian
Journal:  Mol Carcinog       Date:  1991       Impact factor: 4.784

8.  A molecular signature of gastric metaplasia arising in response to acute parietal cell loss.

Authors:  Koji Nozaki; Masako Ogawa; Janice A Williams; Bonnie J Lafleur; Vivian Ng; Ronny I Drapkin; Jason C Mills; Stephen F Konieczny; Sachiyo Nomura; James R Goldenring
Journal:  Gastroenterology       Date:  2007-12-04       Impact factor: 22.682

9.  Identification of stem cells in small intestine and colon by marker gene Lgr5.

Authors:  Nick Barker; Johan H van Es; Jeroen Kuipers; Pekka Kujala; Maaike van den Born; Miranda Cozijnsen; Andrea Haegebarth; Jeroen Korving; Harry Begthel; Peter J Peters; Hans Clevers
Journal:  Nature       Date:  2007-10-14       Impact factor: 49.962

10.  Stimulation of MMP-7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration.

Authors:  Lydia E Wroblewski; P-J M Noble; Adelina Pagliocca; D Mark Pritchard; C Anthony Hart; Fiona Campbell; Andrew R Dodson; Graham J Dockray; Andrea Varro
Journal:  J Cell Sci       Date:  2003-07-15       Impact factor: 5.285

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  85 in total

1.  A chief source of cancer and repair in stomachs.

Authors:  Megan D Radyk; Jason C Mills
Journal:  EMBO J       Date:  2017-06-30       Impact factor: 11.598

2.  Stomach: A chief role for Lgr5+ cells.

Authors:  Katrina Ray
Journal:  Nat Rev Gastroenterol Hepatol       Date:  2017-06-21       Impact factor: 46.802

3.  Injury, repair, inflammation and metaplasia in the stomach.

Authors:  Anne R Meyer; James R Goldenring
Journal:  J Physiol       Date:  2018-03-24       Impact factor: 5.182

Review 4.  Are Gastric and Esophageal Metaplasia Relatives? The Case for Barrett's Stemming from SPEM.

Authors:  Ramon U Jin; Jason C Mills
Journal:  Dig Dis Sci       Date:  2018-08       Impact factor: 3.199

5.  Lgr5+ pericentral hepatocytes are self-maintained in normal liver regeneration and susceptible to hepatocarcinogenesis.

Authors:  Chow Hiang Ang; Shih Han Hsu; Fusheng Guo; Chong Teik Tan; Victor C Yu; Jane E Visvader; Pierce K H Chow; Nai Yang Fu
Journal:  Proc Natl Acad Sci U S A       Date:  2019-09-05       Impact factor: 11.205

Review 6.  Acid and the basis for cellular plasticity and reprogramming in gastric repair and cancer.

Authors:  José B Sáenz; Jason C Mills
Journal:  Nat Rev Gastroenterol Hepatol       Date:  2018-02-21       Impact factor: 46.802

7.  Stem cells in 2017: Digesting recent stem cell advances in the gut.

Authors:  Nick Barker
Journal:  Nat Rev Gastroenterol Hepatol       Date:  2018-01-04       Impact factor: 46.802

8.  Regenerative proliferation of differentiated cells by mTORC1-dependent paligenosis.

Authors:  Spencer G Willet; Mark A Lewis; Zhi-Feng Miao; Dengqun Liu; Megan D Radyk; Rebecca L Cunningham; Joseph Burclaff; Greg Sibbel; Hei-Yong G Lo; Valerie Blanc; Nicholas O Davidson; Zhen-Ning Wang; Jason C Mills
Journal:  EMBO J       Date:  2018-02-21       Impact factor: 11.598

Review 9.  Metaplasia: tissue injury adaptation and a precursor to the dysplasia-cancer sequence.

Authors:  Veronique Giroux; Anil K Rustgi
Journal:  Nat Rev Cancer       Date:  2017-09-01       Impact factor: 60.716

10.  Tropism for Spasmolytic Polypeptide-Expressing Metaplasia Allows Helicobacter pylori to Expand Its Intragastric Niche.

Authors:  José B Sáenz; Nancy Vargas; Jason C Mills
Journal:  Gastroenterology       Date:  2018-10-01       Impact factor: 22.682

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