Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen) and rest (telogen) enabled by the stem cell niche within the hair follicle bulge region, regulated by a mesenchymal component the dermal papilla (DP). It is known that the DP is central to hair follicle regulation, however signalling pathways in the DP are complex and not well understood. Expression array analyses of the DP and STAT5 knockout studies suggest that STAT5 may play an important role in the regulation of hair follicle cycling by the DP. We aimed to investigate STAT5 activation within the DP during hair follicle development and cycling.
STAT5 activation in the DP was characterised through immunofluorescence staining of mouse back skin during hair follicle development and cycling. Back skin was obtained from Topflash transgenic mice, a canonical Wnt reporter transgenic mouse driving luciferase expression, using beta-catenin activity to monitor hair cycling via live bioluminescence imaging. Hair regeneration assays were performed with DP cells using skin-derived precursor(SKP) culture with STAT5 activity modified through adenovirus constructs.
While embryonic skin did not display any activation of STAT5, during postnatal hair follicle development (P0-P19), the majority of phospho-STAT5-positive DP were present within telogen phase, to a lesser extent within catagen and none during anagen. Adult skin showed phospho-STAT5 activation beginning in mid-telogen and persisting until anagen. Staining intensity increased from mid-telogen through to early anagen. Characterisation of SOCS2 by immunofluorescence, a downstream STAT5 transcriptional target, showed expression corresponding to the chronology of phospho-STAT5 activity. SKPs transduced with constitutively-active STAT5 adenovirus constructs were confirmed to have increased STAT5 activity through a casein promoter luciferase reporter assay. Hair regeneration assays demonstrated that SKPs transduced with constitutively-active STAT5 were significantly better at integrating and forming hair follicle DP than control SKPs transduced with GFP alone.
STAT5 activation may act as a mesenchymal switch to improve hair inductive potential and induce natural anagen entry following the first hair follicle cycle.