Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro
Open accessAbstract
The study of gastric epithelial homeostasis and cancer has been hampered by the lack of stem cell markers and in vitro culture methods. The Wnt target gene Lgr5 marks stem cells in the small intestine, colon, and hair follicle. Here, we investigated Lgr5 expression in the stomach and assessed the stem cell potential of the Lgr5(+ve) cells by using in vivo lineage tracing. In neonatal stomach, Lgr5 was expressed at the base of prospective corpus and pyloric glands, whereas expression in the adult was predominantly restricted to the base of mature pyloric glands. Lineage tracing revealed these Lgr5(+ve) cells to be self-renewing, multipotent stem cells responsible for the long-term renewal of the gastric epithelium. With an in vitro culture system, single Lgr5(+ve) cells efficiently generated long-lived organoids resembling mature pyloric epithelium. The Lgr5 stem cell marker and culture method described here will be invaluable tools for accelerating research into gastric epithelial renewal, inflammation/infection, and cancer.
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Tissues including small intestine, colon, stomach, esophagus, tongue, liver, lung, pancreas, heart, ear, and skin have been obtained from iPSCs, adult or fetal cells, either stem/progenitor cells or differentiated cells.
“Under defined physicochemical conditions, tissues such as small intestine7, colon30,31, stomach32,33, esophagus30, tongue34, liver35–38, lung15, pancreas39–41, heart42, ear43, and skin44 have been obtained from iPSCs, adult or fetal cells, either stem/progenitor cells or differentiated cells.”
From Organoids (2022) · cites this paper as [31]
Organoids of murine intestines, livers, and pancreas were successfully transplanted into mice, and the transplanted organoids could restore organ dysfunction.
“Organoids of murine intestines31, livers35,125,126 and pancreas69,146 were successfully transplanted into mice, and the transplanted organoids could restore organ dysfunction.”
From Organoids (2022) · cites this paper as [31]
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 [30]
Intestinal stem cells retain function during normal aging.
“but they do not show functional decline during normal aging.100”
From Aging of hematopoietic stem cells (2018) · cites this paper as [100]
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Molecular mechanisms of stem/progenitor cell maintenance in the adrenal cortex
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- Authors
- Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., Danenberg, E., van den Brink, S., Korving, J., Abo, A., Peters, P. J., Wright, N., Poulsom, R., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- The Netherlands Cancer Institute (NL)
- Queen Mary University of London (GB)
- Cancer Research UK (GB)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 6
- Issue
- 1
- Pages
- 25-36
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2097387056
- Cited by
- 1,547
- References
- 38
- Citations by year
- 2026: 54 · 2025: 71 · 2024: 91 · 2023: 95 · 2022: 101 · 2021: 128 · 2020: 107 · 2019: 98 · 2018: 112 · 2017: 124 · 2016: 124 · 2015: 95 · 2014: 92 · 2013: 93 · 2012: 75
- FWCI
- 39.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1329 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome Trust (104151)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- Lgr5, gastric stem cells, self-renewal, pyloric glands, organoids, in vitro culture, lineage tracing, Wnt signaling, gastric cancer, multipotent stem cells
- MeSH terms
- Aging, Animals, Cell Differentiation, Cells, Cultured, Gastric Mucosa, Gene Expression Regulation, Mice, Transgenic, Stem Cells, Stomach, Biomarkers, Cell Lineage, Gene Expression Profiling, Receptors, G-Protein-Coupled, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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