Paracrine TGF-β Signaling Counterbalances BMP-Mediated Repression in Hair Follicle Stem Cell Activation

摘要: Hair follicle (HF) regeneration begins when communication between quiescent epithelial stem cells (SCs) and underlying mesenchymal dermal papillae (DP) generates sufficient activating cues to overcome repressive BMP signals from surrounding niche cells. Here, we uncover a hitherto unrecognized DP transmitter, TGF-β2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration. This signaling is critical: that cannot sense TGF-β exhibit significant delays HF regeneration, whereas exogenous TGF-β2 stimulates vivo vitro. By engineering TGF-β- BMP-reporter mice, show antagonizes but not through competition for limiting Smad4-coactivator. Rather, our microarray, molecular, genetic studies unveil Tmeff1 as direct TGF-β2/Smad2/3 target gene, expressed by activated physiologically relevant restricting lowering thresholds the niche. Connecting activity an SC's response TGF-βs may explain why these factors wield such diverse cellular effects.