title: Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
abstract: 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.
authors.affiliation: Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sato
authors.forename: Robert G
authors.initials: RG
authors.lastname: Vries
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Snippert
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Stange
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Arie
authors.initials: A
authors.lastname: Abo
authors.forename: Pekka
authors.initials: P
authors.lastname: Kujala
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers