Princess Maxima Center for Pediatric Oncology
Lgr5 stem cell based organoids and their applications
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We originally defined Lgr5 as a Wnt target gene, transcribed in colon cancer cells. Two knock-in alleles revealed exclusive expression of Lgr5 in cycling, columnar cells at the crypt base. Using lineage tracing experiments in adult mice, we found that these Lgr5+ve crypt base columnar cells (CBC) generated all epithelial lineages throughout life, implying that they represent the stem cell of the small intestine and colon. Lgr5 was subsequently found to represent an exquisitely specific and almost ‘generic’ marker for stem cells, including in hair follicles, kidney, liver, mammary gland, inner ear tongue and stomach epithelium.
Single sorted Lgr5+ve stem cells can initiate ever-expanding crypt-villus organoids, or so called ‘mini-guts’ in 3D culture. The technology is based on the observation that Lgr5 is the receptor for a potent stem cell growth factor, R-spondin. Similar 3D cultures systems have been developed for the Lgr5+ve stem cells of human stomach, liver, pancreas, prostate and kidney. Using CRISPR/Cas9 technology, genes can be efficiently modified in organoids of various origins.
Hans Clevers obtained his MD degree in 1984 and his PhD degree in 1985 from the University Utrecht, the Netherlands. His postdoctoral work (1986-1989) was done with Cox Terhorst at the Dana-Farber Cancer Institute of the Harvard University, Boston, USA.
From 1991-2002 Hans Clevers was Professor in Immunology at the University Utrecht and, since 2002, Professor in Molecular Genetics. From 2002-2012 he was director of the Hubrecht Institute in Utrecht. From 2012-2015 he was President of the Royal Netherlands Academy of Arts and Sciences (KNAW). Since June 1, 2015 he is director Research of the Princess Maxima Center for pediatric oncology.
Hans Clevers has been a member of the Royal Netherlands Academy of Arts and Sciences since 2000, a member of the American Academy of Arts and Sciences since 2012 and a member of the National Academy of Sciences of the USA since 2014. He is the recipient of several awards, including the Dutch Spinoza Award in 2001, the Swiss Louis Jeantet Prize in 2004, the Memorial Sloan-Kettering Katharine Berkan Judd Award in 2005, the Israeli Rabbi Shai Shacknai Memorial Prize in 2006, the Dutch Josephine Nefkens Prize for Cancer Research and the German Meyenburg Cancer Research Award in 2008, the Dutch Cancer Society Award in 2009, the United European Gastroenterology Federation (UEGF) Research Prize in 2010, the German Ernst Jung-Preis für Medizin in 2011, the French Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize and the Heineken Prize in 2012 and the Breakthrough Prize in Life Sciences in 2013. He obtained an ERC Advanced Investigator grant in 2008. He is Chevalier de la Legion d’Honneur since 2005 and Knight in the Order of the Netherlands Lion since 2012.