《keratinocyte stem cells，label-retaining cells and possible genome protection mechanisms》.pdfVIP

Keratinocyte Stem Cells, Label-Retaining Cells and Possible Genome Protection Mechanisms Christopher S. Potten EpiStem Ltd., Incubator Building, Manchester, UK Stem cells are the crucial cells upon which the entire tissue is dependent. Here we define and discuss what is meant by and known about keratinocyte stem cells. One way in which these cells have been studied is by their ability to retain radioactivity labelled thymidine for long periods of time (label retaining cells, LRCs). The underlying mechanism has been assumed in the past to be slow cycling but a more likely explanation is the selective segregation of old and new DNA strands (Cairns’s hypothesis). Experiments in the small intestine indicate that the stem cells here are selectively sorting their DNA and becoming LRCs. A possible role for p53 in stem cell biology is presented. Key words: DNA strand segregation/epidermal proliferative unit/hair follicle bulge/keratinocyte stem cells/label retaining cells/p53 J Investig Dermatol Symp Proc 9:183 –195, 2004 Skin has evolved to be a tough, flexible, protective barrier. the basal cells are equally efficient in their contribution to The outer layers of the epidermis, the cornified layers, are this regenerative wounding response. For many years, the composed of hard, thin, plates of keratinous material, some- basal layer was regarded as a homogeneous population times referred to as squames, which represent the re- with all cells being equipotential (Fig 1a); however, work in mains of individual cells which are constantly being the early 1970s began to question this model and a more sloughed from the surface. Beneath the cornified layers complex hierarchical, or lineage-based, concept became are several suprabasal strata of meta