Identification of stem cells in small intestine and colon by marker gene Lgr5.
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.
Barker
Nick
N
Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
van Es
Johan H
JH
Kuipers
Jeroen
J
Kujala
Pekka
P
van den Born
Maaike
M
Cozijnsen
Miranda
M
Haegebarth
Andrea
A
Korving
Jeroen
J
Begthel
Harry
H
Peters
Peter J
PJ
Clevers
Hans
H
D000483:Alleles; D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D003106:Colon / Q000166:cytology*; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D019879:Paneth Cells / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
D015415:Biomarkers; C116884:LGR5 protein, human; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled