期刊
THERANOSTICS
卷 7, 期 7, 页码 2078-2091出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.19390
关键词
Human Pluripotent Stem Cells; Cardiomyocytes; Maturation; Metabolomics; Biomarkers
资金
- NIH [R01CA164492, R01EB007534, R01 EY022086]
- National Science Foundation [1547225, 1508950, DMB- 8415048, OIA-9977486, BIR-9214394]
- UW-Madison Stem Cell and Regenerative Medicine Center fellowship
- NIH Chemistry Biology Interface Training Grand [NIGMS T32 GM008505]
- University of Wisconsin
- U.S. Department of Agriculture
- National Institutes of Health [P41GM66326, P41RR02301, P41GM103399, RR02781, RR08438]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1547225] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1508950] Funding Source: National Science Foundation
Cardiovascular disease is a leading cause of death worldwide. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold immense clinical potential and recent studies have enabled generation of virtually pure hPSC-CMs with high efficiency in chemically defined and xeno-free conditions. Despite these advances, hPSC-CMs exhibit an immature phenotype and are arrhythmogenic in vivo, necessitating development of strategies to mature these cells. hPSC-CMs undergo significant metabolic alterations during differentiation and maturation. A detailed analysis of the metabolic changes accompanying maturation of hPSC-CMs may prove useful in identifying new strategies to expedite hPSC-CM maturation and also may provide biomarkers for testing or validating hPSC-CM maturation. In this study we identified global metabolic changes which take place during long-term culture and maturation of hPSC-CMs derived from three different hPSC lines. We have identified several metabolic pathways, including phospholipid metabolism and pantothenate and Coenzyme A metabolism, which showed significant enrichment upon maturation in addition to fatty acid oxidation and metabolism. We also identified increases in glycerophosphocholine and the glycerophosphocholine: phosphocholine ratio as potential metabolic biomarkers of maturation. These biomarkers were also affected in a similar manner during murine heart development in vivo. These results support that hPSC-CM maturation is associated with extensive metabolic changes in metabolic network utilization and understanding the roles of these metabolic changes has the potential to develop novel approaches to monitor and expedite hPSC-CM maturation.
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