Evidence That Myc Activation Depletes the Epidermal Stem Cell Compartment by Modulating Adhesive Interactions with the Local Microenvironment

The study demonstrated that Myc activation in mouse epidermis led to the depletion of the epidermal stem cell compartment by altering adhesive interactions with the local microenvironment. This was evidenced by the transcriptional analysis of over 10,000 genes, revealing that Myc activation induced genes related to RNA and protein synthesis, cell proliferation, and differentiation, while downregulating over 40% of genes associated with cell adhesion and cytoskeleton proteins. These changes impaired keratinocyte adhesion, motility, and wound healing, correlating with decreased expression of extracellular matrix proteins and integrins, and reduced formation of hemidesmosomes and actomyosin cytoskeleton assembly. Consequently, Myc activation prompted stem cell exit and differentiation into sebocytes and interfollicular epidermis at the expense of hair lineages, due to impaired keratinocyte migration necessary for hair differentiation.