Disruption of Smad4 in mouse epidermis leads to depletion of follicle stem cells.
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-beta (TGF-beta) signaling, stimulated the activation of follicle SCs, leading to hyperplasia of interfollicular epidermis (IFE), HFs, and sebaceous glands (SGs). Increased proliferation of follicle SCs ultimately exhausted the SC niche, indicated by the loss of bromodeoxyuridine (BrdU) label-retaining cells (LRCs), loss of keratin 15 (K15), and CD34 expression. In addition, the colony-forming efficiency of Smad4 mutant keratinocytes was significantly decreased. Increased nuclear localization of beta-catenin and increased expression of c-Myc were correlated with the overactivation and depletion of follicle SCs. We concluded that Smad4 plays a pivotal role in follicle SC maintenance.
Yang
Leilei
L
State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China.
Wang
Lijuan
L
Yang
Xiao
X
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D017353:Gene Deletion; D018859:Hair Follicle / Q000473:pathology*; D006984:Hypertrophy; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051901:Smad4 Protein / Q000172:deficiency* / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism
D015415:Biomarkers; D016271:Proto-Oncogene Proteins c-myc; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D051176:beta Catenin