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

Hugo J Snippert, Arnout G Schepers, Johan H van Es, Benjamin D Simons, Hans Clevers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)62-9
Aantal pagina's8
TijdschriftEMBO Reports
Volume15
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - jan 2014

Vingerafdruk

Duik in de onderzoeksthema's van 'Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion'. Samen vormen ze een unieke vingerafdruk.

Citeer dit