PDF(Pubmed)
Abstract：
In vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting that engrafted PSC-derived myogenic cells remodel their transcriptional signature upon interaction within the adult muscle environment. Here, we show that engrafted myogenic progenitors also remodel their metabolic state. Assessment of oxygen consumption revealed that exposure to the adult muscle environment promotes overt changes in mitochondrial bioenergetics, as shown by the substantial suppression of energy requirements in re-isolated iPax3 donor-derived satellite cells compared to their in vitro-generated progenitors. Mass spectrometry-based metabolomic profiling further confirmed the relationship of engrafted iPax3 donor-derived cells to adult satellite cells. The fact that in vitro-generated myogenic progenitors remodel their bioenergetic signature upon in vivo exposure to the adult muscle environment may have important implications for therapeutic applications.
摘要：
体外产生的多能干细胞（PSC）衍生的Pax3诱导的（iPax3）成肌祖细胞显示出胚胎转录特征，但是在雕刻后，重新分离的iPax3供体来源的卫星细胞的轮廓与出生后的卫星细胞相似，表明移植的PSC衍生的肌源性细胞在成年肌肉环境中相互作用后重塑其转录特征。这里,我们显示移植的生肌祖细胞也重塑了它们的代谢状态。耗氧量的评估表明，暴露于成年肌肉环境会促进线粒体生物能学的明显变化，与体外产生的祖细胞相比，重新分离的iPax3供体来源的卫星细胞对能量需求的实质性抑制表明。基于质谱的代谢组学分析进一步证实了移植的iPaX3供体来源的细胞与成年卫星细胞的关系。体外产生的肌原祖细胞在体内暴露于成年肌肉环境后重塑其生物能量特征的事实可能对治疗应用具有重要意义。
