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 and Hans Clevers ()
Additional contact information
Nick Barker: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Johan H. van Es: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Jeroen Kuipers: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Pekka Kujala: The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Maaike van den Born: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Miranda Cozijnsen: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Andrea Haegebarth: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Jeroen Korving: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Harry Begthel: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
Peter J. Peters: The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Hans Clevers: Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands

Nature, 2007, vol. 449, issue 7165, 1003-1007

Abstract: Abstract The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.

Date: 2007
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DOI: 10.1038/nature06196

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