Follicle stem cells (SCs) residing in the bulge region of a hair follicle (HF) can give rise to multiple lineages during the hair cycle and wound healing.The activation and self-renewal of follicle SCs must be tightly regulated to maintain the HF and epidermal homeostasis.Here we show that, in young mice, disruption of epidermal Smad4, the common mediator of transforming growth factor-β (TGF-β) signaling, stimulated the activation of follicle SCs, leading to hyperplasia of interfollicular epidermis (IFE), HFs and sebaceous glands (SGs).