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Peer-reviewedCC BY-NC 4.0iScience

Lipid metabolism remodeling in human cardiomyocyte differentiation and maturation

Abstract

Cardiac development involves extensive metabolic remodeling, yet dynamic changes of endogenous lipid species during human cardiomyocyte (CM) differentiation remain poorly characterized. In this study, we systematically performed high-coverage lipidomic profiling across five consecutive CM differentiation stages, using high-performance liquid chromatography. MYL2 expression confirmed ventricular lineage specification in late-stage CMs. Ceramide levels peaked at the cardiac progenitor cell (CPC) stage, suggesting a stage-specific association with the mesendoderm (MES)-to-CPC transition. Meanwhile, lipid categories such as monosialodihexosylganglioside, phosphatidylcholine (PC), lysophosphatidylcholine, and lysophosphatidic acid were markedly elevated in mature CMs. Integrated transcriptomic and chromatin accessibility analyses further delineated the temporal regulatory landscape underlying stage-dependent lipid remodeling during cardiogenic differentiation. Functional assays revealed that PC promotes the expression of mature CM marker genes and improves CM viability. Collectively, these findings establish a comprehensive, high-resolution dynamic lipidomic atlas of in vitro hESC-derived CM differentiation, providing a valuable resource for understanding lipid-associated mechanisms in heart development.

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BibTeX
@article{tang2026lipid,
  title = {{Lipid metabolism remodeling in human cardiomyocyte differentiation and maturation}},
  author = {Haite Tang and Raina Liu and Zhiqiang Xiong and Qiqi He and Gang Lu and Wai-Yee Chan and Wuming Wang},
  journal = {iScience},
  year = {2026},
  month = oct,
  doi = {10.1016/j.isci.2026.117821},
  url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03202-5},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Lipid metabolism remodeling in human cardiomyocyte differentiation and maturation
AU  - Haite Tang
AU  - Raina Liu
AU  - Zhiqiang Xiong
AU  - Qiqi He
AU  - Gang Lu
AU  - Wai-Yee Chan
AU  - Wuming Wang
PY  - 2026
DA  - 2026/10/09
JO  - iScience
DO  - 10.1016/j.isci.2026.117821
UR  - https://www.cell.com/iscience/fulltext/S2589-0042(26)03202-5
AB  - Cardiac development involves extensive metabolic remodeling, yet dynamic changes of endogenous lipid species during human cardiomyocyte (CM) differentiation remain poorly characterized. In this study, we systematically performed high-coverage lipidomic profiling across five consecutive CM differentiation stages, using high-performance liquid chromatography. MYL2 expression confirmed ventricular lineage specification in late-stage CMs. Ceramide levels peaked at the cardiac progenitor cell (CPC) stage, suggesting a stage-specific association with the mesendoderm (MES)-to-CPC transition. Meanwhile, lipid categories such as monosialodihexosylganglioside, phosphatidylcholine (PC), lysophosphatidylcholine, and lysophosphatidic acid were markedly elevated in mature CMs. Integrated transcriptomic and chromatin accessibility analyses further delineated the temporal regulatory landscape underlying stage-dependent lipid remodeling during cardiogenic differentiation. Functional assays revealed that PC promotes the expression of mature CM marker genes and improves CM viability. Collectively, these findings establish a comprehensive, high-resolution dynamic lipidomic atlas of in vitro hESC-derived CM differentiation, providing a valuable resource for understanding lipid-associated mechanisms in heart development.
SN  - 2589-0042
ER  -