Constitutive Stat3 activation alters behavior of hair follicle stem and progenitor cell populations.

Abstract

STATs play crucial roles in a wide variety of biological functions, including development, proliferation, differentiation and migration as well as in cancer development. In the present study, we examined the impact of constitutive activation of Stat3 on behavior of keratinocytes, including keratinocyte stem cells (KSC) in vivo. BK5.Stat3C transgenic (Tg) mice, which express a constitutively active form of Stat3 (Stat3C) in the basal layer of the epidermis and in the bulge region KSCs exhibited a significantly reduced number of CD34+/α6 integrin+ cells compared to non-transgenic (NTg) littermates. There was a concomitant increase in the Lgr-6, Lrig-1, and Sca-1 populations in the Tg mice in contrast to the CD34 and Keratin-15 positive population. In addition, increased expression of c-myc, β-catenin, and epithelial-mesenchymal transition (EMT)-related genes as well as decreased expression of α6-integrin was observed in the hair follicles of Tg mice. Notably, Sca-1 was found to be a direct transcriptional target of Stat3 in keratinocytes. The current data suggest that elevated Stat3 activity leads to depletion of hair follicle KSCs along with a concomitant increase of stem/progenitor cells above the bulge region. Overall, the current data indicate that Stat3 plays an important role in keratinocyte stem/progenitor cell homeostasis.