The role of Stem cell antigen-1/Lymphocyte antigen 6A-2/6E-1 knock out in murine epidermis

Abstract Stem Cell Antigen-1 (SCA-1) is a central positive marker for isolating stem cells in several tissues in the mouse. However, for the epidermis, this appears to be the opposite since lack of SCA-1 has been shown to identify keratinocyte populations with progenitor characteristics. This study investigates the effect of SCA-1 knockout in murine keratinocytes. We compared Sca-1EGFP/EGFP knockout and wildtype mice with respect to the three-dimensional morphology of the epidermis, performed functional assays, and generated gene expression profiles on FACS sorted cells. There were no morphological abnormalities on skin, fur, or hair follicles in transgenic knockout mice compared to wild type mice. SCA-1 knockout keratinocytes showed significantly reduced colony-forming efficiency, colony size and proliferation rate in vitro, however, SCA-1 knockout did not alter wound healing efficiency or keratinocyte proliferation rate in vivo. Moreover, gene expression profiling shows that the effect from knockout of SCA-1 in keratinocytes is dissimilar from what has been observed in other tissues. Additionally, tumor assay indicated that SCA-1 knockout decreases the number of formed papillomas. The results indicate a more complex role for SCA-1, which might differ between epidermal keratinocytes during homeostasis and activated conditions.