Abstract: Series 111, Lecture 2

The Harvey Lectures Series 111 (2015—2016)

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Lecture #2: Thursday, November 19, 2015 — Watch Video of Lecture

Lgr5 Stem Cells in Self-Renewal and Cancer

Hans Clevers, MD, PhD

Hans Clevers, MD, PhD

Professor of Molecular Genetics

Hubrecht Institute

Utrecht, The Netherlands

Dr Clevers's Website

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We originally defined Lgr5 as a Wnt target gene, transcribed in colon cancer cells. Two knock-in alleles revealed exclusive expression of Lgr5 in cycling, columnar cells at the crypt base. Using lineage tracing experiments in adult mice, we found that these Lgr5+ve crypt base columnar cells (CBC) generated all epithelial lineages throughout life, implying that they represent the stem cell of the small intestine and colon. Lgr5 was subsequently found to represent an exquisitely specific and almost 'generic' marker for stem cells, including in hair follicles, kidney, liver, mammary gland, inner ear tongue and stomach epithelium.