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

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1038/nature11965

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R. C., Carey, V. J., Bates, D. M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 12,082
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
limma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796
Identification of stem cells in small intestine and colon by marker gene Lgr5
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., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Summaries of Affymetrix GeneChip probe level data
Irizarry, R. A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng015 · Cited by 4,837
Bioinformatics and Computational Biology Solutions Using R and Bioconductor
Gentleman, R. C., Carey, V. J., Huber, W. K., Irizarry, R. A., & Dudoit, S. (2005) · Statistics in the health sciences · doi:10.1007/0-387-29362-0 · Cited by 3,470
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells
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., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt
Potten, C. S., & Loeffler, M. (1990) · Development · doi:10.1242/dev.110.4.1001 · Cited by 1,793

Show all 39 references

Sorted by citations

Items 701–759 of 759

Peer Review #2 of "Cell kinetics during regeneration in the sponge Halisarca caerulea: how local is the response to tissue damage? (v0.1)"
(2015) · PeerJ · doi:10.7287/peerj.820v0.1/reviews/2
Stem Cells in the Body
Slack, J. M. W. (2017) · Wiley eBooks · doi:10.1002/9781119235293.ch10
Faculty Opinions recommendation of BMP restricts stemness of intestinal Lgr5+ stem cells by directly suppressing their signature genes.
Li, L. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727174751.793554910
Faculty Opinions recommendation of Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells.
Li, L. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727748600.793554891
Faculty Opinions recommendation of Phospho-regulation of ATOH1 Is Required for Plasticity of Secretory Progenitors and Tissue Regeneration.
Li, L. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733789469.793554894
Notch-1 mediates Epithelial-Mucosal Healing during Murine Colitis Recovery PhasePreprint
Luthra, L., Patel, S. R., Bian, Z., Liu, Y., Merlin, D., & Garg, P. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.13.496012 · Cited by 1
Scarless Wound Healing
Sanyal, S. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.105618
Dual states of Bmi1-expressing intestinal stem cells drive epithelial development and tissue regenerationPreprint
Smith, N. R., Sengupta, S. K., Conley, P., Giske, N. R., Klocke, C. D., Walker, B. S., McPhail, N., Swain, J. R., Yoo, Y. J., Anderson, A. N., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.30.509798
Cellular Heterogeneity during Metastatic Colonization of Colorectal Cancer
Heinz, M. C. (2022) · Utrecht University Repository (Utrecht University) · doi:10.33540/1556
Efeito do desmame precoce sobre marcadores moleculares e desenvolvimento da mucosa intestinal.
da Costa, A. V. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2021.tde-28012022-155015
Data from Deciphering the Role of Intestinal Crypt Cell Populations in Resistance to Chemotherapy
Frau, C., Jamard, C., Delpouve, G., Guardia, G. D. A., Machon, C., Pilati, C., Nevé, C. L., Laurent‐Puig, P., Guitton, J., Galante, P. A. F., et al. (2023) · doi:10.1158/0008-5472.c.6512431
Data from Deciphering the Role of Intestinal Crypt Cell Populations in Resistance to Chemotherapy
Frau, C., Jamard, C., Delpouve, G., Guardia, G. D. A., Machon, C., Pilati, C., Nevé, C. L., Laurent‐Puig, P., Guitton, J., Galante, P. A. F., et al. (2023) · doi:10.1158/0008-5472.c.6512431.v1
Data from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions
Nimmakayala, R. K., Rauth, S., Venkata, R. C., Marimuthu, S., Nallasamy, P., Vengoji, R., Lele, S. M., Rachagani, S., Mallya, K. B., Malafa, M. P., et al. (2023) · doi:10.1158/1078-0432.c.6530751
Data from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions
Nimmakayala, R. K., Rauth, S., Venkata, R. C., Marimuthu, S., Nallasamy, P., Vengoji, R., Lele, S. M., Rachagani, S., Mallya, K. B., Malafa, M. P., et al. (2023) · doi:10.1158/1078-0432.c.6530751.v1
Effect of cellular dedifferentiation on the growth of cell lineages
Yan, K., Wang, M., Hu, F., & Xu, M. (2023) · Physica A Statistical Mechanics and its Applications · doi:10.1016/j.physa.2023.129306
Noncoding RNA regulatory networks, epigenetics, and programming stem cell renewal and differentiation
Mahnke, A. H., Rouzer, S. K., Tseng, A. M., Salem, N. A., & Miranda, R. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-21863-7.00015-9
Dual States of Bmi1-Expressing Intestinal Stem Cells Drive Epithelial DevelopmentPreprint
Smith, N. R., Sengupta, S. K., Giske, N. R., Conley, P., Klocke, C. D., McPhail, N., Swain, J. R., Yoo, Y. J., Nair, A., Anderson, A. N., et al. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4661071
MODULATION OF IMMUNITY AND BARRIER FUNCTION IN PRE- AND POSTNATAL ANIMAL ONTOGENESIS. THE ROLE OF ENTEROCYTES IN THE INTESTINAL BARRIER FUNCTION MAINTAINING DURING THE FETAL PERIOD OF ANIMAL ONTOGENESIS
Masiuk, D. M., Nedzvetsky, V. S., & Кокарєв, А. В. (2023) · doi:10.30525/978-9934-26-395-8-15
MODULATION OF IMMUNITY AND BARRIER FUNCTION IN PRE- AND POSTNATAL ANIMAL ONTOGENESIS. IMMUNOTROPIC CHEMICALS EFFECT ON THE PIGLET POSTNATAL DEVELOPMENT
Masiuk, D. M., Nedzvetsky, V. S., & Кокарєв, А. В. (2023) · doi:10.30525/978-9934-26-395-8-14
Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties
Shin, J. H., Park, J., Lim, J., Jeong, J., Dinesh, R. K., Maher, S. E., Kim, J., Park, S. Y., Hong, J. Y., Wysolmerski, J. J., et al. (2024) · eLife · doi:10.7554/elife.97279.3
Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell propertiesPreprint
Shin, J. H., Park, J., Lim, J., Jeong, J., Dinesh, R. K., Maher, S. E., Hong, J. Y., Wysolmerski, J. J., Choi, J., & Bothwell, A. L. M. (2024) · eLife · doi:10.7554/elife.97279.1
Recent advances in the interaction between microbiota and intestinal stem cells regulating intestinal development in young animals
LiMei, D. A. I., Deng, Y., YunLong, M. E. N. G., Tan, B., Yin, Y., Ming, Q. I., & Jing, W. A. N. G. (2024) · Scientia Sinica Vitae · doi:10.1360/ssv-2024-0076
Intestinal stem cell renewal controlled by capillary morphogenesis gene 2 following injuryPreprint
Bracq, L. J., Chuat, A., Kunz, B., Burri, O., Guiet, R., & van der Goot, F. G. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.07.631493
Epigenetic fluidity meets phenotypic malleability in intestinal epithelial cells
Bhattacharya, S., & Shivdasani, R. A. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.02.007
Identification of potential necroinflammation-associated necroptosis-related biomarkers in necrotizing enterocolitis based on bioinformatics analysis and machine learning
Zhu, J., Qu, X., Liu, Y., Wang, Y., & Liu, Z. (2025) · Translational Pediatrics · doi:10.21037/tp-2025-247
Innate Immunity and Inflammation
McKarns, S. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.50005-9
Transcriptome of the Murine Duodenum during Recovery after a Lethal Dose of Total Body Irradiation
He, L., Bhat, K., & Pajonk, F. (2025) · Journal of Radiation Protection and Research · doi:10.14407/jrpr.2025.00108
Additional file 1 of Radiation-induced toxicity in rectal epithelial stem cell contributes to acute radiation injury in rectum
Tirado, F. R., Bhanja, P., Castro‐Nallar, E., Olea, X. D., Salamanca, C., & Saha, S. (2021) · Figshare · doi:10.6084/m9.figshare.13585352
Additional file 1 of Evidence for close molecular proximity between reverting and undifferentiated cells
Zreika, S., Fourneaux, C., Vallin, E., Modolo, L., Seraphin, R., Moussy, A., Ventre, E., Bouvier, M., Ozier‐Lafontaine, A., Bonnaffoux, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20252770
Maternal Organ Growth: How the Adult Intestine Remodels During Pregnancy and Lactation
Ameku, T. (2025) · Development Growth & Differentiation · doi:10.1111/dgd.70037
Single-nucleus multi-omics analysis of mouse small-intestinal Lgr5+ cell populations reveals Foxa3-induced Paneth cell-lineage differentiation
Deng, X., Sun, S., Lu, C., Du, H., You, X., Huang, F., Gong, K., Guo, J., Gong, Y., Li, R., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-09736-2
Recherche de nouveaux déterminants génétiques et épigénétiques de susceptibilité à la tumorigenèse intestinale au moyen du modèle murin Apcd14
Quesada, S. (2013) · theses.fr (ABES) · doi:10.70675/5ca6f4fez5c06z4eb3zb5b7z0cffd3b770d8
Régulation des cellules initiatrices de tumeurs dans le cancer colorectal par la Progastrine
Giraud, J. (2013) · theses.fr (ABES) · doi:10.70675/4e0f05c4z6aaez40faz89a5z451a3e609f9b
Loss of cyclin A2 contributes to colorectal carcinogenesis by disrupting colonic homeostasis and inducing inflammation in mice
Guo, Y. (2018) · theses.fr (ABES) · doi:10.70675/378e5eb7zd921z4f49z849cz258dce58c0a9
Regulation of adult muscle stem cell quiescence by Notch signalling
Baghdadi, M. B. (2017) · theses.fr (ABES) · doi:10.70675/2a40b20ezc69ez48a6z85a8zebfe9a7bcccf
Reconstitution de l’architecture thymique et de la différenciation des cellules T dans les immunodéficiences génétiques : développement de stratégies thérapeutiques ciblant directement le thymus
Pouzolles, M. (2018) · theses.fr (ABES) · doi:10.70675/57d4755ez8727z422fz9a97z33a1f70f7216
Impact of microbiota on intestinal stem cells survival after irradiation
Lévy, A. (2018) · theses.fr (ABES) · doi:10.70675/b6ab24a4zf5fdz489ezb1b1za2f33c2c0847
Rôles de l’autophagie dans l'homéostasie des cellules souches intestinales
Trentesaux, C. (2018) · theses.fr (ABES) · doi:10.70675/6bad110bz19b1z4cd6z81d0z74d0fb1e27f3
La signalisation insuline comme garant de la fonction barrière intestinale
Gueddouri, D. (2021) · theses.fr (ABES) · doi:10.70675/8371f5a7zb0c3z4f82z83e9z236d0eedb3f1
Etude de la régulation transcriptionnelle de la différenciation des cellules entéroendocrines dans un modèle d'organoïde intestinal humain
Giethlen, C. (2019) · theses.fr (ABES) · doi:10.70675/124d9f75z3ecbz4db0z8ea8z9813fa536613
Etude fonctionnelle de Shavenbaby dans l'homéostasie du système rénal chez la drosophile
Bohère, J. (2017) · theses.fr (ABES) · doi:10.70675/15b59f44z4d2dz40d9z9f65z8da38a2b131a
Etude des mécanismes impliqués dans le contrôle du destin des cellules souches intestinales et développement d'un modèle 3D d'épithélium intestinal
Creff, J. (2019) · theses.fr (ABES) · doi:10.70675/43618074z8731z4146zbc02z93e942398468
Contrôle de l'homéostasie épithéliale intestinale par la dynamique des isoformes du variant d'histone H2A.Z
Rispal, J. (2020) · theses.fr (ABES) · doi:10.70675/4a1dc94dzc25bz4007z952cz1d4dccdde1e8
Effet des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile
Jneid, R. (2021) · theses.fr (ABES) · doi:10.70675/7780fc44z241cz4a6fz95bez2efbc90bd685
Α-gustducine intestinale : implication dans l'obésité et le diabète de type 2
Gléau, L. L. (2021) · theses.fr (ABES) · doi:10.70675/dc436e75zb6d2z4bb4zb9a1z17b025f205a6
Characterizing the role of epithelial cells at transition zones in normal and disease state
Mitoyan, L. (2021) · theses.fr (ABES) · doi:10.70675/ddf25abazea11z4dd1za773zea6476b58547
In situ study of the dynamic transfer of encapsulated active molecules : application to the passage of a model barrier
Peyret, C. (2024) · theses.fr (ABES) · doi:10.70675/a935a9adz1eedz4ccdz84c5z9cb33dd26d87
A velocity-informed framework for resolving functional stratification in rare human stem cells
Jarczak, J., Ratajczak, M. Z., & Kucia, M. (2026) · Leukemia · doi:10.1038/s41375-026-02956-9
Nuclear Receptor Liver Receptor Homolog-1 drives Intestinal Stem Cell regeneration and UPR/ER stress response after gut injuryPreprint
Chen, H.-J., Braverman, K. N., Yu, B., & Bayrer, J. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.15.725547
A progenitor cell population contributes to prenatal injury repair and neonatal antimicrobial defense in the small intestine
Shen, Y., Li, C., Zhang, H., Liu, H., Zhao, L., & Chen, Y. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117503
Akkermansia muciniphila : a member of the gut microbiota that modulates intestinal stem cell function
Stein, R. A., Ganesh, A., Rianom, N. A., & Paratore, A. W. (2026) · Physiological Genomics · doi:10.1152/physiolgenomics.00230.2025
From mice to humans—divergent strategies for intestinal homeostasis and regeneration
Ishikawa, K., Sugimoto, S., & Sato, T. (2026) · FEBS Letters · doi:10.1002/1873-3468.70387 · Cited by 2
Melatonin-inspired hybrid spheroids accelerate intestinal repair via YAP-driven fetal reprogramming
Seo, Y., Ahn, J., Nguyen, N.-N., Lee, H. S., Lee, Y., Kim, S. H., Yu, J. H., Yang, J.-W., Park, H.-J., Lee, H., et al. (2026) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2026.101176
Regenerative Inflammation in IBD: How Type I Interferons and TNF Cross-Talk Converts Epithelial Repair into Therapeutic Response
Hinton, E., Kemp, R. A., Schultz, M., & Gadeock, S. (2026) · Cells · doi:10.3390/cells15131144
Self-citation
Patient-derived organoids for precision oncology in colorectal cancer: from tumor modeling to clinical translation
Lupo, B., Catalano, I., & Trusolino, L. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02747-x
Oncofetal reprogramming and cellular plasticity in colorectal cancer: from mechanisms to clinical translation
Wang, H., Liu, S., Zhang, M., Deng, C., & Han, Z. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1912866
Building and regenerating intestines by manipulating intestinal stem cells
Kuo, C. J., Blutt, S. E., Donowitz, M., Estes, M. K., Guha, C., Klein, O. D., Li, L., Niland, J. C., Santos, A. J. M., Shivdasani, R. A., et al. (2026) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-026-01242-4 · Cited by 1
Zebrafish sox9b+ cells function as intestinal stem cells for epithelial homeostasis and regeneration
Wu, G., Wei, X., Zhang, L., Huang, B., Fu, J., Zhao, J., Huang, Y., Tan, X., Ma, X., Fu, X., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117964
Cell plasticity in cancer and therapy resistance
Seo, Y., Jang, J., & Park, J. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01869-y · Cited by 1

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

About these checks

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Intestinal label-retaining cells are secretory precursors expressing Lgr5

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks