Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion.

EMBO Reports
Hugo J SnippertHans Clevers

Abstract

The concept of 'field cancerization' describes the clonal expansion of genetically altered, but morphologically normal cells that predisposes a tissue to cancer development. Here, we demonstrate that biased stem cell competition in the mouse small intestine can initiate the expansion of such clones. We quantitatively analyze how the activation of oncogenic K-ras in individual Lgr5(+) stem cells accelerates their cell division rate and creates a biased drift towards crypt clonality. K-ras mutant crypts then clonally expand within the epithelium through enhanced crypt fission, which distributes the existing Paneth cell niche over the two new crypts. Thus, an unequal competition between wild-type and mutant intestinal stem cells initiates a biased drift that leads to the clonal expansion of crypts carrying oncogenic mutations.

References

Jun 1, 1990·Cell·E R Fearon, B Vogelstein
Sep 1, 1988·The New England Journal of Medicine·B VogelsteinJ L Bos
Jun 1, 1986·Biophysical Journal·M Bjerknes
Feb 21, 1996·Journal of Theoretical Biology·M Bjerknes
Jan 10, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Emma MarshmanChristopher S Potten
Jan 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Laura C GreavesStuart A C McDonald
Sep 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Owen J SansomAlan R Clarke
Sep 24, 2008·Annual Review of Physiology·Laurens G van der Flier, Hans Clevers
Dec 19, 2008·Nature·Nick BarkerHans Clevers
Oct 12, 2010·Science·Carlos Lopez-GarciaDouglas J Winton
Aug 10, 2011·Future Oncology·Trevor A GrahamNicholas A Wright

❮ Previous
Next ❯

Citations

Mar 8, 2014·Cellular and Molecular Life Sciences : CMLS·Maria SirakovMichelina Plateroti
Feb 9, 2016·Current Biology : CB·Saskia J E SuijkerbuijkEugenia Piddini
Jan 20, 2016·Science·Margaret A Goodell, Thomas A Rando
Sep 4, 2015·The Journal of Pathology·Elena VetterWolfgang Zimmermann
Jun 17, 2015·Stem Cell Research·Jessica J GierutKevin M Haigis
Mar 5, 2015·Cell Metabolism·Jacqueline A KoehlerDaniel J Drucker
Sep 26, 2015·Science·Iñigo Martincorena, Peter J Campbell
Dec 7, 2014·Cell Stem Cell·Ann ZeunerRuggero De Maria
Jul 22, 2014·The Journal of Pathology·Julia FredePhilip H Jones
May 27, 2014·Gastroenterology·Bon-Kyoung Koo, Hans Clevers
Apr 8, 2016·Journal of the Royal Society, Interface·Patrick Smadbeck, Michael P H Stumpf
Jun 26, 2015·British Journal of Cancer·D J Huels, O J Sansom
Feb 25, 2014·Seminars in Cancer Biology·Shawna Tan, Nick Barker
May 11, 2015·Cell Stem Cell·Giacomo Donati, Fiona M Watt
Jan 8, 2015·Frontiers in Oncology·Michael J GerdesFiona Ginty
Feb 27, 2015·PLoS Computational Biology·Benjamin AllenMartin A Nowak
Jun 30, 2016·Cancers·Felipe de Sousa E Melo, Louis Vermeulen
Jul 31, 2016·Current Opinion in Cell Biology·Steffen Rulands, Benjamin D Simons
Jul 28, 2016·Nature·Adriana Sánchez-DanésCédric Blanpain
Aug 19, 2016·Journal of the Royal Society, Interface·Torsten ThalheimJoerg Galle
Aug 9, 2016·Annual Review of Cell and Developmental Biology·Cristina Clavería, Miguel Torres
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jared M FischerR Michael Liskay
Dec 3, 2016·Toxicology Letters·Juliana Yumi SakitaVinicius Kannen
Apr 19, 2016·United European Gastroenterology Journal·Isadora RosaAntónio D Pereira
Feb 9, 2017·Nature Reviews. Gastroenterology & Hepatology·Chang-Ho R ChoiTrevor A Graham
Jul 30, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Claire FalandryEric Gilson
Feb 27, 2016·Scientific Reports·Marc LeushackeCarmen Pin
Mar 10, 2017·The Journal of Biological Chemistry·Joshua C SnyderMarc G Caron
May 30, 2017·Gastroenterology·Lotte BruensHugo J Snippert
Apr 24, 2018·Molecular Biology and Evolution·Vincent L Cannataro, Jeffrey P Townsend
Dec 30, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Carmen PinToshiro Sato
Dec 9, 2017·Nature Reviews. Cancer·Kit CurtiusTrevor A Graham
Jun 1, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yoshitatsu SeiStephen A Wank
May 26, 2018·Annual Review of Nutrition·Salvador Alonso, Ömer H Yilmaz
Mar 1, 2014·Nature Cell Biology·Axel BehrensBjörn Schumacher
Mar 27, 2019·Molecular Biology and Evolution·Bingjie ChenChung-I Wu
May 2, 2019·Protein & Cell·Tomoaki HishidaJuan Carlos Izpisua Belmonte
Sep 3, 2014·The EMBO Journal·Edward R Morrissey, Louis Vermeulen
Aug 15, 2015·The EMBO Journal·Elise S DemitrackLinda C Samuelson

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy

Software Mentioned

Confetti

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.