期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 115, 期 3, 页码 630-644出版社
WILEY
DOI: 10.1002/bit.26504
关键词
3D aggregates; fluxome; human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs); metabolic maturation; transcriptome
资金
- Fundacao para a Ciencia e Tecnologia (FCT) [HMSP-ICT/0039/2013]
- CARDIOSTEM [MITPTB/ECE/0013/2013]
- NETDIAMOND [SAICTPAC/0047/2015]
- FEEI [Lisboa2020, FCT/POCI-01-0145-FEDER-016385]
- iNOVA4Health Research Unit [LISBOA-01-0145-FEDER-007344]
Three-dimensional (3D) cultures of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) hold great promise for drug discovery, providing a better approximation to the in vivo physiology over standard two-dimensional (2D) monolayer cultures. However, the transition of CM differentiation protocols from 2D to 3D cultures is not straightforward. In this work, we relied on the aggregation of hPSC-derived cardiac progenitors and their culture under agitated conditions to generate highly pure cardiomyocyte aggregates. Whole-transcriptome analysis and C-13-metabolic flux analysis allowed to demonstrate at both molecular and fluxome levels that such 3D culture environment enhances metabolic maturation of hiPSC-CMs. When compared to 2D, 3D cultures of hiPSC-CMs displayed down-regulation of genes involved in glycolysis and lipid biosynthesis and increased expression of genes involved in OXPHOS. Accordingly, 3D cultures of hiPSC-CMs had lower fluxes through glycolysis and fatty acid synthesis and increased TCA-cycle activity. Importantly, we demonstrated that the 3D culture environment reproducibly improved both CM purity and metabolic maturation across different hPSC lines, thereby providing a robust strategy to derive enriched hPSC-CMs with metabolic features closer to that of adult CMs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据