PMID- 19329995 OWN - NLM STAT- MEDLINE DCOM- 20090630 LR - 20240104 IS - 1476-4687 (Electronic) IS - 0028-0836 (Linking) VI - 459 IP - 7244 DP - 2009 May 14 TI - Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. PG - 262-5 LID - 10.1038/nature07935 [doi] AB - The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5(+) stem cells can also initiate these cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche. FAU - Sato, Toshiro AU - Sato T AD - Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands. FAU - Vries, Robert G AU - Vries RG FAU - Snippert, Hugo J AU - Snippert HJ FAU - van de Wetering, Marc AU - van de Wetering M FAU - Barker, Nick AU - Barker N FAU - Stange, Daniel E AU - Stange DE FAU - van Es, Johan H AU - van Es JH FAU - Abo, Arie AU - Abo A FAU - Kujala, Pekka AU - Kujala P FAU - Peters, Peter J AU - Peters PJ FAU - Clevers, Hans AU - Clevers H LA - eng PT - Journal Article DEP - 20090329 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Lgr5 protein, mouse) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Receptors, Notch) SB - IM MH - Animals MH - Cell Culture Techniques/*methods MH - Cell Lineage MH - Cell Separation MH - Gene Expression Regulation, Developmental MH - Intestinal Mucosa/metabolism MH - Intestines/*anatomy & histology/*cytology MH - Mesoderm/cytology/metabolism MH - Mice MH - Multipotent Stem Cells/cytology/metabolism MH - Organoids/*cytology/growth & development/metabolism MH - Paneth Cells/metabolism MH - Receptors, G-Protein-Coupled/*metabolism MH - Receptors, Notch/metabolism MH - Regeneration MH - Stem Cell Niche MH - Stem Cells/*cytology/*metabolism EDAT- 2009/03/31 09:00 MHDA- 2009/07/01 09:00 CRDT- 2009/03/31 09:00 PHST- 2008/07/16 00:00 [received] PHST- 2009/02/24 00:00 [accepted] PHST- 2009/03/31 09:00 [entrez] PHST- 2009/03/31 09:00 [pubmed] PHST- 2009/07/01 09:00 [medline] AID - nature07935 [pii] AID - 10.1038/nature07935 [doi] PST - ppublish SO - Nature. 2009 May 14;459(7244):262-5. doi: 10.1038/nature07935. Epub 2009 Mar 29.