Endo- and Exometabolome Crosstalk in Mesenchymal Stem Cells Undergoing Osteogenic Differentiation.

Endo- and Exometabolome Crosstalk in Mesenchymal Stem Cells Undergoing Osteogenic Differentiation.
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骨髓间充质干细胞成骨分化过程中的内代谢组和外代谢组交叉。

DOI:
10.3390/cells11081257
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发表时间:
2022-04-07
期刊:
影响因子:
6
通讯作者:
Gil, Ana M.
Gil, Ana M.
中科院分区:
生物学2区
文献类型:
--
作者:
Bispo, Daniela S. C.;Michalkova, Lenka;Correia, Marlene;Jesus, Catarina S. H.;Duarte, Iola F.;Goodfellow, Brian J.;Oliveira, Mariana B.;Mano, Joao F.;Gil, Ana M.

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据我们所知,本文首次描述了使用核磁共振(NMR)波谱对人类脂肪组织干细胞(hAMSC)成骨分化的脂质组和外代谢组表征。 NMR 的整体性质使得能够跟踪胆固醇、单不饱和脂肪酸和多不饱和脂肪酸(包括 ω-6 和 ω-3 脂肪酸)、几种磷脂(磷脂酰胆碱、磷脂酰乙醇胺、鞘磷脂和缩醛磷脂)以及甘油单酯和甘油三酯的时程演变。脂质变化几乎完全发生在第 1 天和第 7 天之间,随后在第 7 天后出现脂质组稳定的趋势。平均而言,磷脂和更长且更多的不饱和脂肪酸在第 7 天之前增加,可能与质膜流动性有关。脂质组变化与先前报道的极性内代谢组分析和本文报道的相同细胞中的外代谢组变化的结合,使得在 hAMSC 成骨分化过程中建立重要的相关性。我们的结果支持了与膜重塑动力学、抗氧化机制、蛋白质合成和能量代谢相关的假设。重要的是,对特定摄取或排泄代谢物的观察为识别可用于优化成骨方案的潜在骨诱导代谢物铺平了道路。
This paper describes, for the first time to our knowledge, a lipidome and exometabolome characterization of osteogenic differentiation for human adipose tissue stem cells (hAMSCs) using nuclear magnetic resonance (NMR) spectroscopy. The holistic nature of NMR enabled the time-course evolution of cholesterol, mono- and polyunsaturated fatty acids (including ω-6 and ω-3 fatty acids), several phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens), and mono- and triglycerides to be followed. Lipid changes occurred almost exclusively between days 1 and 7, followed by a tendency for lipidome stabilization after day 7. On average, phospholipids and longer and more unsaturated fatty acids increased up to day 7, probably related to plasma membrane fluidity. Articulation of lipidome changes with previously reported polar endometabolome profiling and with exometabolome changes reported here in the same cells, enabled important correlations to be established during hAMSC osteogenic differentiation. Our results supported hypotheses related to the dynamics of membrane remodelling, anti-oxidative mechanisms, protein synthesis, and energy metabolism. Importantly, the observation of specific up-taken or excreted metabolites paves the way for the identification of potential osteoinductive metabolites useful for optimized osteogenic protocols.
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