Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells
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Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5(hi) stem cells persist life-long, yet crypts drift toward clonality within a period of 1-6 months. We have collected short- and long-term clonal tracing data of individual Lgr5(hi) cells. These reveal that most Lgr5(hi) cell divisions occur symmetrically and do not support a model in which two daughter cells resulting from an Lgr5(hi) cell division adopt divergent fates (i.e., one Lgr5(hi) cell and one transit-amplifying [TA] cell per division). The cellular dynamics are consistent with a model in which the resident stem cells double their numbers each day and stochastically adopt stem or TA fates. Quantitative analysis shows that stem cell turnover follows a pattern of neutral drift dynamics.
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Lineage tracing the progeny of Wnt1+ progenitors confirmed a common progenitor pool that can give rise to both epithelial and neuronal cells.
“We confirmed our hypothesis of a common progenitor pool by lineage tracing the progeny of Wnt1+ progenitors (by crossing Wnt1-CRE2 (Lewis et al., 2013) with R26R-Confetti mice (Livet et al., 2007; Snippert et al., 2010), Figure 2H,I.”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Snippert et al., 2010
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- Authors
- Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- Harvard University (US)
- University of Cambridge (GB)
- Corresponding author
- Clevers, Hans
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 143
- Issue
- 1
- Pages
- 134-144
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2168901267
- Cited by
- 1,951
- References
- 49
- Citations by year
- 2026: 74 · 2025: 115 · 2024: 108 · 2023: 96 · 2022: 113 · 2021: 133 · 2020: 157 · 2019: 126 · 2018: 175 · 2017: 134 · 2016: 133 · 2015: 115 · 2014: 129 · 2013: 137 · 2012: 105
- FWCI
- 44.40
- 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, 1056 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 (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Funders
- Engineering and Physical Sciences Research Council (EP/F043325/1, EP/F032773/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- intestinal stem cells, Lgr5, symmetric cell division, clonal expansion, neutral drift, transit amplifying cells, fate mapping, Paneth cells, small intestine
- MeSH terms
- Animals, Clone Cells, Intestine, Small, Models, Biological, Stem Cells, Cell Lineage, Receptors, G-Protein-Coupled, Mice
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