PSC 来源的成肌骨骼祖细胞体内成熟过程中的代谢变化。

Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors.

机构信息

Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.

出版信息

Cells. 2023 Dec 29;13(1):76. doi: 10.3390/cells13010076.

DOI:10.3390/cells13010076

PMID:38201280

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10778145/

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

体外生成的多能干细胞（PSC）衍生的 Pax3 诱导（iPax3）成肌祖细胞表现出胚胎转录特征，但在植入后，重新分离的 iPax3 供体来源的卫星细胞的特征向类似于出生后卫星细胞的特征变化，这表明植入的 PSC 衍生的成肌细胞在与成人肌肉环境相互作用时重塑其转录特征。在这里，我们表明植入的成肌祖细胞也重塑了它们的代谢状态。对耗氧量的评估表明，暴露于成人肌肉环境会促进线粒体生物能明显变化，这表现为重新分离的 iPax3 供体来源的卫星细胞与体外生成的祖细胞相比，能量需求大大抑制。基于质谱的代谢组学分析进一步证实了植入的 iPax3 供体衍生细胞与成人卫星细胞的关系。事实上，体外生成的成肌祖细胞在体内暴露于成人肌肉环境后重塑其生物能特征，这可能对治疗应用具有重要意义。