Intestinal label-retaining cells are secretory precursors expressing Lgr5
Abstract
The rapid cell turnover of the intestinal epithelium is achieved from small numbers of stem cells located in the base of glandular crypts. These stem cells have been variously described as rapidly cycling or quiescent. A functional arrangement of stem cells that reconciles both of these behaviours has so far been difficult to obtain. Alternative explanations for quiescent cells have been that they act as a parallel or reserve population that replace rapidly cycling stem cells periodically or after injury; their exact nature remains unknown. Here we show mouse intestinal quiescent cells to be precursors that are committed to mature into differentiated secretory cells of the Paneth and enteroendocrine lineage. However, crucially we find that after intestinal injury they are capable of extensive proliferation and can give rise to clones comprising the main epithelial cell types. Thus, quiescent cells can be recalled to the stem-cell state. These findings establish quiescent cells as an effective clonogenic reserve and provide a motivation for investigating their role in pathologies such as colorectal cancers and intestinal inflammation.
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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 [25]
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- Authors
- Buczacki, S. J. A., Zecchini, H. I., Nicholson, A. M., Russell, R., Vermeulen, L., Kemp, R., & Winton, D. J.
- Affiliations
- Cancer Research UK (GB)
- Corresponding author
- Winton, Douglas J.
- Venue
- Nature
- Published
- 2013-02-27
- Volume
- 495
- Issue
- 7439
- Pages
- 65-69
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2119059014
- Semantic Scholar
- 9cc05a3e71ae9af40d9b1e9b30a463e557747415
- Cited by
- 761
- References
- 39
- Citations by year
- 2026: 20 · 2025: 39 · 2024: 35 · 2023: 34 · 2022: 42 · 2021: 65 · 2020: 65 · 2019: 41 · 2018: 85 · 2017: 68 · 2016: 67 · 2015: 73 · 2014: 76 · 2013: 49 · 2012: 2
- FWCI
- 58.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Cancer Research UK (17044, 22310)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- 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
- Keywords
- label-retaining cells, Lgr5, Paneth cells, enteroendocrine cells, intestinal epithelial regeneration, intestinal injury, stem cell niche, lineage tracing, intestinal crypts, colorectal cancer, intestinal inflammation
- MeSH terms
- Animals, Cell Differentiation, Cell Division, Cell Separation, Clone Cells, Intestinal Neoplasms, Intestines, Regeneration, Staining and Labeling, Biomarkers, Cell Lineage, Paneth Cells, Multipotent Stem Cells, Receptors, G-Protein-Coupled, Mice, Stem Cell Niche
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