| First Author | Oshimori N | Year | 2012 |
| Journal | Cell Stem Cell | Volume | 10 |
| Issue | 1 | Pages | 63-75 |
| PubMed ID | 22226356 | Mgi Jnum | J:181500 |
| Mgi Id | MGI:5311524 | Doi | 10.1016/j.stem.2011.11.005 |
| Citation | Oshimori N, et al. (2012) Paracrine TGF-beta signaling counterbalances BMP-mediated repression in hair follicle stem cell activation. Cell Stem Cell 10(1):63-75 |
| abstractText | 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-beta2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration. This signaling is critical: HFSCs that cannot sense TGF-beta exhibit significant delays in HF regeneration, whereas exogenous TGF-beta2 stimulates HFSCs in vivo and in vitro. By engineering TGF-beta- and BMP-reporter mice, we show that TGF-beta2 signaling antagonizes BMP signaling in HFSCs but not through competition for limiting Smad4-coactivator. Rather, our microarray, molecular, and genetic studies unveil Tmeff1 as a direct TGF-beta2/Smad2/3 target gene, expressed by activated HFSCs and physiologically relevant in restricting and lowering BMP thresholds in the niche. Connecting BMP activity to an SC's response to TGF-betas may explain why these signaling factors wield such diverse cellular effects. |
