title: 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.
authors: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors: Simon J A
authors: SJ
authors: Buczacki
authors: Heather Ireland
authors: HI
authors: Zecchini
authors: Anna M
authors: AM
authors: Nicholson
authors: Roslin
authors: R
authors: Russell
authors: Louis
authors: L
authors: Vermeulen
authors: Richard
authors: R
authors: Kemp
authors: Douglas J
authors: DJ
authors: Winton
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002469:Cell Separation; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000473:pathology; D007422:Intestines / Q000166:cytology / Q000293:injuries / Q000473:pathology; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019879:Paneth Cells / Q000166:cytology* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012038:Regeneration; D013194:Staining and Labeling; D055153:Stem Cell Niche
chemical_list: D015415:Biomarkers; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled