Impact of Stat3 Deletion or Activation on Keratinocyte Stem/Progenitor Cells

The study investigated the role of Stat3 in keratinocyte behavior, particularly focusing on keratinocyte stem cells (KSCs). In K5.Stat3C transgenic mice, which express an active form of Stat3, there was a reduction in CD34+ve/alpha 6 integrin +ve cells and an increase in progenitor populations, suggesting that Stat3 activation induced KSCs to exit their niche. Stat3C overexpression did not alter differentiation markers in the interfollicular epidermis but was associated with increased β-catenin and decreased α6-integrin, potentially facilitating cell migration. Conversely, Stat3 deletion in K5.Cre X Stat3fl/fl mice led to increased differentiation marker expression and progenitor gene expression after TPA treatment, indicating that Stat3 deletion promoted differentiation. These findings suggested that Stat3 played a crucial role in keratinocyte differentiation and migration, with implications for epithelial carcinogenesis.