Identification of stem cells in small intestine and colon by marker gene Lgr5
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.
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Aging does not significantly change the number of Lgr5-EGFP-positive crypts, the percentage of Lgr5 EGFPhi cells, or the total number of Lgr5EGFPhi ISCs in mice.
“we did not observe a significant change in the number of crypts positive for Lgr5-EGFP (Figures 2A and 2B) as well as in the percentage of Lgr5 EGFPhi cells (as determined by flow cytometric analyses) (Figure S2A) as well as for the total number of Lgr5EGFPhi ISCs (Figure 2C) at the crypt base at positions 0 to +4 (Barker et al., 2007) in aged compared to young animals.”
From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Barker et al., 2007
The ability to form organoids depends primarily on ISC function.
“The ability to form organoids depends primarily on ISC function (Barker et al., 2007; Sato et al., 2009).”
From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Barker et al., 2007
Interconversion between reserve and active intestinal stem cell populations occurs.
“interconversion of reserve and active intestinal stem cell (ISC) populations has also been observed previously25,28–30.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [29]
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References 32 · Cited by 5,687
- Authors
- Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., & Clevers, H.
- Affiliations
- Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Clevers, Hans
- Venue
- Nature
- Published
- 2007-10
- Volume
- 449
- Issue
- 7165
- Pages
- 1003-1007
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1982603620
- Cited by
- 5,687
- References
- 32
- Citations by year
- 2026: 229 · 2025: 303 · 2024: 328 · 2023: 330 · 2022: 366 · 2021: 394 · 2020: 374 · 2019: 343 · 2018: 341 · 2017: 353 · 2016: 296 · 2015: 322 · 2014: 333 · 2013: 321 · 2012: 308
- FWCI
- 67.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- Lgr5, intestinal stem cells, small intestine, colon, crypt base columnar cells, Wnt signaling, lineage tracing, stem cell markers, cancer stem cells, colon cancer, intestinal epithelial regeneration, pluripotent stem cells
- MeSH terms
- Alleles, Animals, Colon, Humans, Intestine, Small, Stem Cells, Biomarkers, Genes, Reporter, Paneth Cells, Gene Expression Profiling, Receptors, G-Protein-Coupled, Cell Line, Tumor, Mice
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