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Updated: Apr 6, 2026
Generating Self-Assembling Human Heart Organoids Derived from Pluripotent Stem Cells
Published on: September 15, 2021
Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells
Cathelijne W van den Berg1, Satoshi Okawa2, Susana M Chuva de Sousa Lopes1
1Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
Insights
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show immature gene expression profiles. Benchmarking against human fetal heart development reveals hPSC-CMs resemble early fetal stages, maturing towards later fetal stages with specific culture conditions.
Area of Science:
- Cardiology
- Stem Cell Biology
- Developmental Biology
Background:
- Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit immature functional and molecular characteristics compared to adult cardiomyocytes.
- Limited data exists on gene expression profiles of the developing human fetal heart across different developmental stages.
Purpose of the Study:
- To characterize gene expression profiles of the human fetal heart during the first and second trimesters.
- To establish a developmental benchmark for assessing the maturity of hPSC-CMs.
- To identify chamber-specific and stage-specific gene expression patterns in the developing human heart.
Main Methods:
- Collection of matched ventricular and atrial samples from human fetuses across the first and second trimesters.
- Comprehensive gene expression analysis of isolated heart chambers.
- Comparative analysis of fetal heart gene expression data with hPSC-CM gene expression profiles.
Main Results:
- hPSC-CMs display gene expression profiles akin to first-trimester fetal heart tissue.
- Maturation culture conditions shift hPSC-CM gene expression profiles closer to second-trimester fetal heart samples.
- Identification of distinct gene expression signatures for different heart chambers and developmental stages.
Conclusions:
- Human fetal heart gene expression data provides a valuable reference for benchmarking hPSC-CM maturity.
- The study contributes to understanding human heart development and provides a framework for assessing stem cell-derived cardiac cells.
- Gene expression profiling offers insights into the developmental trajectory of hPSC-CMs.
Abstract:
Differentiated derivatives of human pluripotent stem cells (hPSCs) are often considered immature because they resemble foetal cells more than adult, with hPSC-derived cardiomyocytes (hPSC-CMs) being no exception. Many functional features of these cardiomyocytes, such as their cell morphology, electrophysiological characteristics, sarcomere organization and contraction force, are underdeveloped compared with adult cardiomyocytes. However, relatively little is known about how their gene expression profiles compare with the human foetal heart, in part because of the paucity of data on the human foetal heart at different stages of development. Here, we collected samples of matched ventricles and atria from human foetuses during the first and second trimester of development. This presented a rare opportunity to perform gene expression analysis on the individual chambers of the heart at various stages of development, allowing us to identify not only genes involved in the formation of the heart, but also specific genes upregulated in each of the four chambers and at different stages of development. The data showed that hPSC-CMs had a gene expression profile similar to first trimester foetal heart, but after culture in conditions shown previously to induce maturation, they cluster closer to the second trimester foetal heart samples. In summary, we demonstrate how the gene expression profiles of human foetal heart samples can be used for benchmarking hPSC-CMs and also contribute to determining their equivalent stage of development.
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