PMID- 23446353 OWN - NLM STAT- MEDLINE DCOM- 20130326 LR - 20240210 IS - 1476-4687 (Electronic) IS - 0028-0836 (Linking) VI - 495 IP - 7439 DP - 2013 Mar 7 TI - Intestinal label-retaining cells are secretory precursors expressing Lgr5. PG - 65-9 LID - 10.1038/nature11965 [doi] AB - 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. FAU - Buczacki, Simon J A AU - Buczacki SJ AD - Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. FAU - Zecchini, Heather Ireland AU - Zecchini HI FAU - Nicholson, Anna M AU - Nicholson AM FAU - Russell, Roslin AU - Russell R FAU - Vermeulen, Louis AU - Vermeulen L FAU - Kemp, Richard AU - Kemp R FAU - Winton, Douglas J AU - Winton DJ LA - eng SI - GEO/GSE43772 GR - 17044/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130227 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Biomarkers) RN - 0 (Lgr5 protein, mouse) RN - 0 (Receptors, G-Protein-Coupled) SB - IM CIN - Nature. 2013 Mar 7;495(7439):53-4. doi: 10.1038/nature11958. PMID: 23446347 CIN - Nat Rev Mol Cell Biol. 2013 Apr;14(4):193. doi: 10.1038/nrm3551. PMID: 23486280 CIN - Cell Stem Cell. 2013 Apr 4;12(4):389-90. doi: 10.1016/j.stem.2013.03.009. PMID: 23561439 CIN - Nat Rev Mol Cell Biol. 2013 Apr;14(4):193. PMID: 23847776 MH - Animals MH - Biomarkers/analysis/metabolism MH - Cell Differentiation MH - Cell Division MH - *Cell Lineage MH - Cell Separation MH - Clone Cells/cytology/metabolism MH - Intestinal Neoplasms/pathology MH - Intestines/cytology/injuries/pathology MH - Mice MH - Multipotent Stem Cells/*cytology/*metabolism MH - Paneth Cells/*cytology/*metabolism MH - Receptors, G-Protein-Coupled/*metabolism MH - Regeneration MH - Staining and Labeling MH - Stem Cell Niche EDAT- 2013/03/01 06:00 MHDA- 2013/03/27 06:00 CRDT- 2013/03/01 06:00 PHST- 2012/07/26 00:00 [received] PHST- 2013/01/30 00:00 [accepted] PHST- 2013/03/01 06:00 [entrez] PHST- 2013/03/01 06:00 [pubmed] PHST- 2013/03/27 06:00 [medline] AID - nature11965 [pii] AID - 10.1038/nature11965 [doi] PST - ppublish SO - Nature. 2013 Mar 7;495(7439):65-9. doi: 10.1038/nature11965. Epub 2013 Feb 27.