CD133 determines epithelial stem cell activation

Objectives: Stem cells are a valuable resource to counteract disease progression as well as aid in tissue regeneration. Despite these important capabilities, little is known on how stem cells quiescence and cell cycle entry are regulated. CD133, a five transmembrane protein has been widely used as a potent stem cell marker. However, the function of this molecule has not yet been elucidated. Our study aims to connect the function of CD133 with the molecular dynamics of cell cycle progression in stem cells.
Methods: 3D immunofluorescence analysis on wild type and CD133 knock out mouse incisor was used to monitor epithelial stem cell status dynamics in the presence or absence of CD133 and the effect on the activation of stem cells. The cell cycle was analysed using a modified fluorescent cell cycle indicator system. In vitro real time RT-PCR, western blotting and colonigenic growth analysis of established mouse incisor epithelial stem cell lines were used to confirm in vivo findings. PCR array as well as Co-IP and ChIP analysis were applied to investigate the molecular link between molecular pathways and stem cell dynamics.
Results: Our results show that CD133 plays a centrol role in controlling stem cell activation by integrating different molecular signaling pathways. This molecule is essential for regulating cellular structure changes resulting in cell status changes upon signal stimulation.
Conclusions: CD133 acts as a central molecule affecting multiple aspects of cellular events during stem cell activation. Ultimately, we believe that our results will eventually lead to improved tissue regeneration therapies.