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SUMMARY:Lgr5 Stem Cells in self-renewal and cancer - Hans Clevers\, Hubrec
 ht Institute
DTSTART:20120911T120000Z
DTEND:20120911T133000Z
UID:TALK39471@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The intestinal epithelium is the most rapidly self-renewing ma
 mmalian tissue. Lgr5 is a gene transcribed in cycling\, crypt base columna
 r cells at the crypt base. Using lineage tracing experiments the Lgr5+ve c
 ells were identified as the stem cells of the intestinal epithelium. Furth
 ermore\, Lgr5+ve stem cells can initiate ever-expanding organoids in vitro
 . The Lgr5+ve stem cell hierarchy of differentiation is maintained in thes
 e organoids. Thus\, intestinal crypt-villus units can be built from a sing
 le stem cell in the absence of a non-epithelial cellular niche.\n\nAlthoug
 h\, Lgr5 stem cells persist life-long\, crypts drift toward clonality quic
 kly.  The cellular dynamics are consistent with a model in which the stem 
 cells divide symmetrically\, and stochastically adopt stem or transient am
 plifying cell fates after cell division.\n\nLgr5 stem cells are interspers
 ed between differentiated Paneth cells\, which produce all essential signa
 ls for stem-cell maintenance. Co-culturing of sorted stem cells with Panet
 h cells dramatically improves organoid formation. Genetic removal of Panet
 h cells in vivo results in the concomitant loss of Lgr5 stem cells.\n\nInt
 estinal cancer is initiated by Wnt pathway-activating mutations in genes s
 uch as APC. Deletion of APC in stem cells\, but not in other crypt cells r
 esults in neoplasia\, identifying the stem cell as the cell-of-origin of a
 denomas. Moreover\, a stem cell/progenitor cell hierarchy is maintained in
  stem cell-derived adenomas\, lending support to the “cancer stem cell
 ”-concept. 
LOCATION:Cambridge Research Institute
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