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早期心脏血统期间的代谢重塑多能干细胞的规范

Sunday Ndoma Bobori¹, Yuxiang Zhu¹, Alicia Saarinen¹

¹Departments of Biochemistry and Molecular Biology and Cardiovascular Medicine, Center for Regenerative Biotherapeutics, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.

|October 27, 2023

概括

人类多能干细胞 (PSC) 在心脏发育过程中经历了显著的代谢转变. 大多数代谢变化发生在分化早期,人类PSC衍生心肌细胞 (hPSC-CMs) 的成熟度在第5天以后有限.

科学领域:

心血管生物学心血管生物学
代谢调节代谢调节代谢调节代谢调节
干细胞分化的过程

背景情况:

心脏发育需要大量的代谢重塑,从多能干细胞 (PSC) 的糖解转向成熟心肌细胞的氧化代谢.
了解人类心脏发育中的这种代谢转变的时间动态至关重要,但目前缺乏详细分析.

研究的目的:

为了研究人类PSC衍生的心脏谱系规范期间的时间代谢变化.
描述人类PSC衍生的心肌细胞 (hPSC-CMs) 的代谢表型.

主要方法:

利用动态多重反应监测代谢学来分析人类PSC分化过程中的中央碳代谢.
进行实时代谢分析以评估氧化和糖解速率.

主要成果:

在分化过程中发生了显著的代谢重塑,在多能性和中皮 (1日) 和中皮到早期心脏阶段 (5日) 之间观察到的最明显的变化.
代谢成熟度在第5天之后显示出有限的进展.
hPSC-CMs比PSCs具有更高的氧化代谢,但保留了高的糖解率,表明代谢特征不成熟.

结论:

在早期心脏谱系规范过程中,代谢变化至关重要.
hPSC-CMs的代谢表型表明一种不成熟的状态,突出了优化潜力.
代谢干预可以提高心脏谱系的规范性和hPSC-CM成熟度.

关键词:

3D心肌细胞分化3D心肌细胞分化葡萄糖溶解是什么诱导多能干细胞的诱导干细胞.代谢生物组的代谢生物组氧化代谢的氧化代谢

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