Metabolic Remodeling during Early Cardiac Lineage Specification of Pluripotent Stem Cells.
Metabolic Remodeling during Early Cardiac Lineage Specification of Pluripotent Stem Cells.
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DOI：
10.3390/metabo13101086
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发表时间：
2023-10-17
期刊：
影响因子：
4.1
通讯作者：
Folmes CDL
中科院分区：
文献类型：
--
作者：
Bobori SN;Zhu Y;Saarinen A;Liuzzo AJ;Folmes CDL
越来越多的证据表明，代谢物和能量代谢在调节细胞命运中起着积极而非间接的作用。心脏发育需要剧烈的代谢重塑，从主要依赖多能干细胞（PSC）中的糖酵解到氧化各种能量底物，以满足发育心脏持续收缩的高生物能量需求。然而，缺乏对能量代谢重塑如何促进人类心脏发育的详细分析。使用中心碳代谢的动态多反应监测代谢组学，我们评估了人类PSC 3D心脏谱系特化过程中能量代谢的时间变化。显著的代谢重塑发生在完全分化期间，但时间分析显示，大多数变化发生在从多能性到中胚层（第1天）和中胚层到早期心脏（第5天）的过渡期间，超过第5天心脏代谢的成熟有限。实时代谢分析表明，虽然与PSC相比，hPSC心肌细胞（hPSC-CM）显示出升高的氧化代谢速率，但它们仍然保持高的糖酵解速率，证实了不成熟的代谢表型。这些观察结果支持代谢优化分化过程以支持hPSC-CM的谱系特化和成熟的机会。
Growing evidence indicates that metabolites and energy metabolism play an active rather than consequential role in regulating cellular fate. Cardiac development requires dramatic metabolic remodeling from relying primarily on glycolysis in pluripotent stem cells (PSCs) to oxidizing a wide array of energy substrates to match the high bioenergetic demands of continuous contraction in the developed heart. However, a detailed analysis of how remodeling of energy metabolism contributes to human cardiac development is lacking. Using dynamic multiple reaction monitoring metabolomics of central carbon metabolism, we evaluated temporal changes in energy metabolism during human PSC 3D cardiac lineage specification. Significant metabolic remodeling occurs during the complete differentiation, yet temporal analysis revealed that most changes occur during transitions from pluripotency to mesoderm (day 1) and mesoderm to early cardiac (day 5), with limited maturation of cardiac metabolism beyond day 5. Real-time metabolic analysis demonstrated that while hPSC cardiomyocytes (hPSC-CM) showed elevated rates of oxidative metabolism compared to PSCs, they still retained high glycolytic rates, confirming an immature metabolic phenotype. These observations support the opportunity to metabolically optimize the differentiation process to support lineage specification and maturation of hPSC-CMs.
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影响因子：
1.2
作者：
Pakzad KK;Tan JJ;Anderson S;Board M;Clarke K;Carr CA
通讯作者：
Carr CA
影响因子：
4.6
作者：
通讯作者：
--
影响因子：
--
作者：
Burridge PW;Holmström A;Wu JC
通讯作者：
Wu JC
影响因子：
20.1
作者：
Ebert, Antje;Joshi, Amit U.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
11.8
作者：
DeLaughter, Daniel M.;Bick, Alexander G.;Wakimoto, Hiroko;McKean, David;Gorham, Joshua M.;Kathiriya, Irian S.;Hinson, John T.;Homsy, Jason;Gray, Jesse;Pu, William;Bruneau, Benoit G.;Seidman, J. G.;Seidman, Christine E.
通讯作者：
Seidman, Christine E.