PDF(Pubmed)
Abstract：
Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs; satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here, we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNA-seq (scRNA-seq) to show that MuSCs express low levels of canonical EC markers in mice. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.
摘要：
内皮和骨骼肌谱系产生于常见的胚胎祖细胞。尽管他们共同的发展起源，成人内皮细胞(ECs)和肌肉干细胞(MuSCs)(卫星细胞)被认为具有不同的基因特征和信号通路.在这里，我们通过揭示成年MuSC行为如何受到EC转录本子集表达的影响来改变这种范式。我们使用了几种计算分析，包括单细胞RNAseq，以显示MuSC在小鼠中表达低水平的经典EC标记。我们证明了MuSC的存活受一个这样的原型内皮信号通路(VEGFA-FLT1)的调节。使用药理学和遗传功能增益和丧失研究，我们确定FLT1-AKT1轴是VEGFA介导的MuSC存活调节的关键效应子.一起,我们的数据支持VEGFA-FLT1-AKT1途径促进肌肉再生过程中的MuSC存活，并强调了选择转录物的次要表达如何足以影响细胞行为。
