Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer

The extended longevity of many mammals imposes the need for an effective tissue renewal capacity within the vital organs to maintain optimal function. Resident adult stem cells are instrumental in delivering this renewal capacity by virtue of their characteristic ability to maintain themselves long-term as a population (self-renewal), whilst also supplying all functional cell-lineages of the respective tissue (multipotency). The homeostatic activity of these adult stem cell reservoirs is tailored to meet the specific renewal requirements of individual tissues through a combination of intrinsic genetic programming and local cues delivered from the surrounding environment (the niche). Considerable phenotypic diversity therefore exists between adult stem cell populations in different organs, making it a considerable challenge to identify broadly applicable markers that facilitate their identification and characterization. However, the 7-transmembrane receptor, Lgr5 has recently gained prominence as a marker of Wnt-regulated adult stem cell populations in the hair-follicle, intestine and stomach. A closely-related protein, Lgr6 marks adult stem cells responsible for fueling the renewal of the sebaceous gland and skin. The discovery of these markers has already greatly improved our understanding of stem cell biology in these rapidly renewing tissues and has major implications for the identification and isolation of human adult stem cell populations for exploitation of their regenerative medicine potential in the clinic. Oncogene (2012) 31, 3009-3022; doi: 10.1038/onc.2011.479; published online 17 October 2011