A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

• DOI: 10.1007/s12015-010-9139-0
• Publication Date: 2010-04-07T09:12:16Z
• Authors: Corina Lorz; Ramón García-Escu...; Carmen Segrelles; Marina I. Garín; José M. Ariza; Mirentxu Santos; Sergio Ruiz; María F. Lara; Ana B. Martínez-Cruz; Clotilde Costa; Águeda Buitrago-P...; Cristina Saiz-Ladera; Marta Dueñas; Jesús M. Paramio
• Keywords: 0301 basic medicine; Cancer Research; Gene Expression Profiling; Stem Cells; Cell Biology; Article; Mice; 03 medical and health sciences; Animals; Hair Follicle; Cells, Cultured; Developmental Biology; Signal Transduction

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis.