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SUMMARY:Lgr5 stem cells in self-renewal and cancer - Hans Clevers\, Hubrec
 ht Institute\, The Netherlands
DTSTART:20120911T120000Z
DTEND:20120911T130000Z
UID:TALK38517@talks.cam.ac.uk
CONTACT:29286
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.  Although\
 , Lgr5 stem cells persist life-long\, crypts drift toward clonality quickl
 y.  The cellular dynamics are consistent with a model in which the stem ce
 lls divide symmetrically\, and stochastically adopt stem or transient ampl
 ifying cell fates after cell division.  Lgr5 stem cells are interspersed b
 etween differentiated Paneth cells\, which produce all essential signals f
 or stem-cell maintenance. Co-culturing of sorted stem cells with Paneth ce
 lls dramatically improves organoid formation. Genetic removal of Paneth ce
 lls in vivo results in the concomitant loss of Lgr5 stem cells.\nIntestina
 l cancer is initiated by Wnt pathway-activating mutations in genes such as
  APC. Deletion of APC in stem cells\, but not in other crypt cells results
  in neoplasia\, identifying the stem cell as the cell-of-origin of adenoma
 s. Moreover\, a stem cell/progenitor cell hierarchy is maintained in stem 
 cell-derived adenomas\, lending support to the “cancer stem cell”-conc
 ept. \n
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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