Abstract 4300: Constitutive activation of Stat3 increases hair follicle progenitor population at the expense of bulge region keratinocyte stem cells

Abstract Mouse skin epidermis is maintained throughout life by a highly proliferative compartment located in the outer root sheath called the hair follicle bulge. Stem cells located in the mouse hair follicle bulge region have self-renewing, slow cycling and quiescent characteristics and maintain hair and epidermal growth. In the present study, we examined the impact of Stat3 activation on the number and proliferative capacity of bulge region keratinocyte stem cells (KSCs). K5. Stat3C transgenic mice express a constitutively active/dimerized form of Stat3 called Stat3C via the bovine keratin 5 (K5) promoter. The K5 promoter targets expression of Stat3C in the basal layer of the epidermis as well as in the bulge region KSCs. We analyzed the number of KSCs using the bulge specific stem cell markers CD34 and α6 integrin. The number of CD34+ve/α6 +ve cells was significantly reduced in Stat3C mice as compared to the non-transgenic littermates. Sca-1 positive cells reside in the infundibulum region of the hair follicle. We analyzed the Sca-1 expressing population in the total hair follicle cells and found that the number of Sca-1 expressing cells was increased in the Stat3C mice. Activation of Stat3, in bulge region KSCs appeared to cause epidermal stem cells to exit the stem cell compartment. To understand how Stat3 exerts these effects we studied the expression of Stat3 target genes like Myc and cyclin D1. Both Myc and cyclin D1 were found to be upregulated in total hair follicle cells in the transgenic mice. In addition, the levels of both α6 and β1 integrin were reduced in total hair follicle cells of the Stat3C mice supporting the hypothesis that activation of Stat3 causes stem cell to exit from the bulge region. Overall, these studies suggest that Stat3 is critical for the behavior, growth properties and quiescent characteristics of bulge region KSCs. Supported by NIH Grant CA76520. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4300.