Cited by 761Digestive system and related healthCancer Cells and MetastasisWnt/β-catenin signaling in development and cancer

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Intestinal label-retaining cells are secretory precursors expressing Lgr5

Buczacki, Simon J. A., Zecchini, Heather Ireland, Nicholson, Anna M., Russell, Roslin, Vermeulen, Louis, Kemp, Richard, Winton, Douglas J.·2013·Nature

DOI 10.1038/nature11965

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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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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.
ORCID: Buczacki, Simon J. A.
Vermeulen, Louis
Kemp, Richard
Winton, Douglas J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2013-02-27
Volume: 495
Issue: 7439
Pages: 65-69
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11965
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
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: Health Sciences › Medicine › Gastroenterology › 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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Intestinal label-retaining cells are secretory precursors expressing Lgr5

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