肌肉卫星细胞与血管龛的相互作用通过 VEGF 和 Notch 信号维持静息状态。
Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling.
机构信息
Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA; Paul & Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.
Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA; Paul & Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.
出版信息
Cell Stem Cell. 2018 Oct 4;23(4):530-543.e9. doi: 10.1016/j.stem.2018.09.007.
Skeletal muscle is a complex tissue containing tissue resident muscle stem cells (satellite cells) (MuSCs) important for postnatal muscle growth and regeneration. Quantitative analysis of the biological function of MuSCs and the molecular pathways responsible for a potential juxtavascular niche for MuSCs is currently lacking. We utilized fluorescent reporter mice and muscle tissue clearing to investigate the proximity of MuSCs to capillaries in 3 dimensions. We show that MuSCs express abundant VEGFA, which recruits endothelial cells (ECs) in vitro, whereas blocking VEGFA using both a vascular endothelial growth factor (VEGF) inhibitor and MuSC-specific VEGFA gene deletion reduces the proximity of MuSCs to capillaries. Importantly, this proximity to the blood vessels was associated with MuSC self-renewal in which the EC-derived Notch ligand Dll4 induces quiescence in MuSCs. We hypothesize that MuSCs recruit capillary ECs via VEGFA, and in return, ECs maintain MuSC quiescence though Dll4.
骨骼肌是一种复杂的组织，其中包含组织驻留的肌肉干细胞（卫星细胞）（MuSCs），对于出生后的肌肉生长和再生至关重要。目前缺乏对 MuSCs 的生物学功能以及负责 MuSCs 潜在血管周龛位的分子途径的定量分析。我们利用荧光报告小鼠和肌肉组织透明化技术，从三维角度研究了 MuSCs 与毛细血管的接近程度。我们发现 MuSCs 表达丰富的 VEGFA，它在体外招募内皮细胞（ECs），而使用血管内皮生长因子（VEGF）抑制剂和 MuSC 特异性 VEGFA 基因缺失来阻断 VEGFA 则会降低 MuSCs 与毛细血管的接近程度。重要的是，这种与血管的接近程度与 MuSC 的自我更新有关，其中 EC 衍生的 Notch 配体 Dll4 诱导 MuSC 静止。我们假设 MuSCs 通过 VEGFA 招募毛细血管 ECs，而反过来，ECs 通过 Dll4 维持 MuSC 的静止。
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