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Lgr5+ stem cells in epithelial homeostasis and cancer
We have identified Lgr5 as a facultative component of the Wnt receptor complex specifically expressed on cycling stem cells in the intestine, colon, stomach, hair-follicles, ovary and embryonic kidney. Using a 3D ex vivo culture system, freshly isolated Lgr5+ stem cells spontaneously generate self-organizing, self-renewing epithelial “organoids”, providing a physiological, renewable source of patient epithelia for both research and clinical applications. Employing in vivo clonal fate mapping strategies in the stomach, we further show that a balanced homeostasis of the glandular epithelium and stem cell pools is achieved via neutral competition between symmetrically dividing Lgr5+ stem cells. Long-term ablation of the Lgr5+ cell compartment in vivo severely impairs epithelial homeostasis in both the pyloric antrum and the corpus, establishing the Lgr5+ stem cell pool as being critical for daily maintenance of the gastric mucosa. We additionally characterize the transcriptomes Lgr5+ stem cells in mouse intestine, colon and stomach, revealing new gastric stem cell-specific markers that can be used to isolate human gastric stem cells for regenerative medicine applications and for use in selectively targeting cancer-causing mutations to the Lgr5+ stem cell compartment in mice as a means of evaluating their contribution to gastric cancer initiation and progression.
Date:
14 August 2015, 13:00
Venue:
MRC Weatherall Institute of Molecular Medicine, Headington OX3 9DS
Venue Details:
Seminar room
Speaker:
Professor Nicholas Barker (Institute of Medical Biology, Singapore)
Organising department:
MRC Weatherall Institute of Molecular Medicine
Organiser:
Liz Rose (University of Oxford, Weatherall Institute of Molecular Medicine)
Organiser contact email address:
liz.rose@imm.ox.ac.uk
Host:
Professor Doug Higgs (MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital)
Part of:
WIMM Occasional Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Liz Rose
