Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
EMBO J. 2023 May 15;42(10):e112196. doi: 10.15252/embj.2022112196. Epub 2023 Mar 30.
Blood vessels can play dual roles in tissue growth by transporting gases and nutrients and by regulating tissue stem cell activity via signaling. Correlative evidence implicates skin endothelial cells (ECs) as signaling niches of hair follicle stem cells (HFSCs), but functional demonstration from gene depletion of signaling molecules in ECs is missing to date. Here, we show that depletion of the vasculature-factor Alk1 increases BMP4 secretion from ECs, which delays HFSC activation. Furthermore, while previous evidence suggests a lymphatic vessel role in adult HFSC activation possibly through tissue drainage, a blood vessel role has not yet been addressed. Genetic perturbation of the ALK1-BMP4 axis in all ECs or the lymphatic ECs specifically unveils inhibition of HFSC activation by blood vessels. Our work suggests a broader relevance of blood vessels, adding adult HFSCs to the EC functional repertoire as signaling niches for the adult stem cells.
血管在组织生长中具有双重作用，既能通过运输气体和营养物质，也能通过信号转导调节组织干细胞的活性。相关证据表明皮肤内皮细胞（ECs）是毛囊干细胞（HFSCs）的信号龛，但迄今为止，还缺乏通过 ECs 中信号分子的基因缺失来进行功能验证的证据。在这里，我们发现血管因子 Alk1 的缺失会增加 ECs 中 BMP4 的分泌，从而延迟 HFSC 的激活。此外，虽然之前的证据表明淋巴管在成体 HFSC 激活中可能具有通过组织引流的作用，但血管的作用尚未得到解决。在所有 EC 或特定的淋巴管 EC 中对 ALK1-BMP4 轴进行遗传干扰，揭示了血管对 HFSC 激活的抑制作用。我们的工作表明，血管具有更广泛的相关性，将成体 HFSC 添加到 EC 的功能谱中，作为成体干细胞的信号龛。
