Stem Cells and Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris 75015, France; CNRS UMR 3738, Institut Pasteur, Paris 75015, France; Sorbonne Universités, UPMC, University of Paris 06, IFD-ED 515, Paris 75252, France.
Bioimaging and Optics platform (BIOP), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Cell Stem Cell. 2018 Dec 6;23(6):859-868.e5. doi: 10.1016/j.stem.2018.09.017. Epub 2018 Nov 8.
Critical features of stem cells include anchoring within a niche and activation upon injury. Notch signaling maintains skeletal muscle satellite (stem) cell quiescence by inhibiting differentiation and inducing expression of extracellular components of the niche. However, the complete spectrum of how Notch safeguards quiescence is not well understood. Here, we perform Notch ChIP-sequencing and small RNA sequencing in satellite cells and identify the Notch-induced microRNA-708, which is a mirtron that is highly expressed in quiescent cells and sharply downregulated in activated cells. We employ in vivo and ex vivo functional studies, in addition to live imaging, to show that miR-708 regulates quiescence and self-renewal by antagonizing cell migration through targeting the transcripts of the focal-adhesion-associated protein Tensin3. Therefore, this study identifies a Notch-miR708-Tensin3 axis and suggests that Notch signaling can regulate satellite cell quiescence and transition to the activation state through dynamic regulation of the migratory machinery.
干细胞的关键特征包括在龛位内的锚定和损伤后的激活。Notch 信号通过抑制分化并诱导龛位细胞外成分的表达来维持骨骼肌卫星（干）细胞静止。然而，Notch 如何保护静止状态的完整范围尚不清楚。在这里，我们在卫星细胞中进行 Notch ChIP-seq 和小 RNA 测序，并鉴定出 Notch 诱导的 microRNA-708，这是一种在静止细胞中高度表达并在激活细胞中急剧下调的 mirtron。我们采用体内和体外功能研究，以及实时成像，表明 miR-708 通过靶向粘着斑相关蛋白 Tensin3 的转录本来调节通过细胞迁移来调节静止和自我更新。因此，本研究确定了一个 Notch-miR708-Tensin3 轴，并表明 Notch 信号可以通过动态调节迁移机制来调节卫星细胞静止和向激活状态的转变。
