Journal ArticleDOI
Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium.
Toshiro Sato,Daniel E. Stange,Marc Ferrante,Marc Ferrante,Robert G.J. Vries,Johan H. van Es,Stieneke van den Brink,Winan J. van Houdt,Apollo Pronk,Joost van Gorp,Peter D. Siersema,Hans Clevers +11 more
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TLDR
A technology that can be used to study infected, inflammatory, or neoplastic tissues from the human gastrointestinal tract is developed that might have applications in regenerative biology through ex vivo expansion of the intestinal epithelia.About:
This article is published in Gastroenterology.The article was published on 2011-11-01. It has received 2726 citations till now. The article focuses on the topics: Human gastrointestinal tract & Adult stem cell.read more
Citations
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Journal ArticleDOI
Modeling Development and Disease with Organoids
TL;DR: 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina, and hold promise to predict drug response in a personalized fashion.
Journal ArticleDOI
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
Marc van de Wetering,Hayley E. Francies,Joshua M. Francis,Joshua M. Francis,Gergana Bounova,Francesco Iorio,Apollo Pronk,Winan J. van Houdt,Joost van Gorp,Amaro Taylor-Weiner,Lennart Kester,Anne McLaren-Douglas,Joyce Blokker,Sridevi Jaksani,Sina Bartfeld,Richard Volckman,Peter van Sluis,Vivian S. W. Li,Sara Seepo,Chandra Sekhar Pedamallu,Chandra Sekhar Pedamallu,Kristian Cibulskis,Scott L. Carter,Scott L. Carter,Aaron McKenna,Michael S. Lawrence,Lee Lichtenstein,Chip Stewart,Jan Koster,Rogier Versteeg,Alexander van Oudenaarden,Julio Saez-Rodriguez,Robert G.J. Vries,Gad Getz,Gad Getz,Lodewyk F. A. Wessels,Michael R. Stratton,Ultan McDermott,Matthew Meyerson,Matthew Meyerson,Mathew J. Garnett,Hans Clevers +41 more
TL;DR: Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations and may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design.
Journal ArticleDOI
Organoid Models of Human and Mouse Ductal Pancreatic Cancer
Sylvia F. Boj,Chang-Il Hwang,Chang-Il Hwang,Lindsey A. Baker,Lindsey A. Baker,Iok In Christine Chio,Iok In Christine Chio,Dannielle D. Engle,Dannielle D. Engle,Vincenzo Corbo,Vincenzo Corbo,Myrthe Jager,Mariano Ponz-Sarvise,Mariano Ponz-Sarvise,Hervé Tiriac,Hervé Tiriac,Mona S. Spector,Mona S. Spector,Ana Gracanin,Tobiloba E. Oni,Tobiloba E. Oni,Tobiloba E. Oni,Kenneth H. Yu,Ruben van Boxtel,Meritxell Huch,Keith Rivera,John P. Wilson,Michael E. Feigin,Michael E. Feigin,Daniel Öhlund,Daniel Öhlund,Abram Handly-Santana,Abram Handly-Santana,Christine M. Ardito-Abraham,Christine M. Ardito-Abraham,Michael Ludwig,Michael Ludwig,Ela Elyada,Ela Elyada,Brinda Alagesan,Brinda Alagesan,Brinda Alagesan,Giulia Biffi,Giulia Biffi,Georgi N. Yordanov,Georgi N. Yordanov,Bethany Delcuze,Bethany Delcuze,Brianna Creighton,Brianna Creighton,Kevin Wright,Kevin Wright,Young-Kyu Park,Young-Kyu Park,Folkert H.M. Morsink,I. Quintus Molenaar,Inne H.M. Borel Rinkes,Edwin Cuppen,Yuan Hao,Ying Jin,Isaac J. Nijman,Christine A. Iacobuzio-Donahue,Steven D. Leach,Darryl J. Pappin,Molly Hammell,David S. Klimstra,Olca Basturk,Ralph H. Hruban,G. J. A. Offerhaus,Robert G.J. Vries,Hans Clevers,David A. Tuveson,David A. Tuveson,David A. Tuveson +73 more
TL;DR: Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression that demonstrate that organoids are a facile model system to discover characteristics of this deadly malignancy.
Journal ArticleDOI
A Landscape of Pharmacogenomic Interactions in Cancer
Francesco Iorio,Francesco Iorio,Theo A. Knijnenburg,Theo A. Knijnenburg,Daniel J. Vis,Graham R. Bignell,Michael P. Menden,Michael P. Menden,Michael Schubert,Nanne Aben,Nanne Aben,Emanuel Gonçalves,Syd Barthorpe,Howard Lightfoot,Thomas Cokelaer,Thomas Cokelaer,Patricia Greninger,Ewald van Dyk,Han Chang,Heshani de Silva,Holger Heyn,Xianming Deng,Regina K. Egan,Qingsong Liu,Tatiana Mironenko,Xeni Mitropoulos,Laura Richardson,Jinhua Wang,Tinghu Zhang,Sebastian Moran,Sergi Sayols,Maryam Soleimani,David Tamborero,Nuria Lopez-Bigas,Nuria Lopez-Bigas,Petra Ross-Macdonald,Manel Esteller,Manel Esteller,Nathanael S. Gray,Daniel A. Haber,Daniel A. Haber,Michael R. Stratton,Cyril H. Benes,Lodewyk F. A. Wessels,Lodewyk F. A. Wessels,Julio Saez-Rodriguez,Julio Saez-Rodriguez,Ultan McDermott,Mathew J. Garnett +48 more
TL;DR: It is reported how cancer-driven alterations identified in 11,289 tumors from 29 tissues can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs.
Journal ArticleDOI
SARS-CoV-2 productively infects human gut enterocytes.
Mart M. Lamers,Joep Beumer,Jelte van der Vaart,Kèvin Knoops,Jens Puschhof,Tim I Breugem,Raimond B. G. Ravelli,J. Paul van Schayck,Anna Z Mykytyn,Hans Duimel,Elly van Donselaar,Samra Riesebosch,Helma J.H. Kuijpers,Debby Schipper,Willine J. van de Wetering,Miranda de Graaf,Marion Koopmans,Edwin Cuppen,Peter J. Peters,Bart L. Haagmans,Hans Clevers +20 more
TL;DR: It is demonstrated that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut, and hSIOs serve as an experimental model for coronavirus infection and biology.
References
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Journal ArticleDOI
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
Toshiro Sato,Robert G.J. Vries,Hugo J. Snippert,Marc van de Wetering,Nick Barker,Daniel E. Stange,Johan H. van Es,Arie Abo,Pekka Kujala,Peter J. Peters,Hans Clevers +10 more
TL;DR: It is concluded that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
Journal ArticleDOI
Identification of stem cells in small intestine and colon by marker gene Lgr5
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 +10 more
TL;DR: The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers, suggesting that it represents the stem cell of the small intestine and colon.
Journal ArticleDOI
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Toshiro Sato,Johan H. van Es,Hugo J. Snippert,Daniel E. Stange,Robert G.J. Vries,Maaike van den Born,Nick Barker,Noah F. Shroyer,Marc van de Wetering,Hans Clevers +9 more
TL;DR: It is concluded that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell, in colon crypts, and co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation.
Journal ArticleDOI
Crypt stem cells as the cells-of-origin of intestinal cancer
Nick Barker,Rachel A. Ridgway,Johan H. van Es,Marc van de Wetering,Harry Begthel,Maaike van den Born,Esther Danenberg,Alan Richard Clarke,Owen J. Sansom,Hans Clevers +9 more
TL;DR: It is concluded that stem-cell-specific loss of Apc results in progressively growing neoplasia in long-lived intestinal stem cells.
Journal ArticleDOI
The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
Marc van de Wetering,Elena Sancho,Cornelis Verweij,Wim de Lau,Irma Oving,Adam Hurlstone,Karin van der Horn,Eduard Batlle,Damien Coudreuse,Anna-Pavlina G. Haramis,Menno Tjon-Pon-Fong,Petra Moerer,Maaike van den Born,Gwen Soete,Steven T. Pals,Martin Eilers,René H. Medema,Hans Clevers +17 more
TL;DR: The β-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells.
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