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Updated: Aug 30, 2025
Generation of First Heart Field-like Cardiac Progenitors and Ventricular-like Cardiomyocytes from Human Pluripotent Stem Cells
Published on: June 19, 2018
Modeling human multi-lineage heart field development with pluripotent stem cells
Donghe Yang1, Juliana Gomez-Garcia2, Shunsuke Funakoshi3
1McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Insights
Researchers modeled human heart development using human pluripotent stem cells (hPSCs). This study identified distinct cardiac cell lineages and revealed conserved developmental programs between humans and mice for heart development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Cardiovascular Research
Background:
- Mammalian heart development involves distinct cardiomyocyte (CM) subtypes originating from first heart field (FHF), anterior second heart field (aSHF), and posterior second heart field (pSHF) lineages.
- Understanding human embryonic cardiogenesis is crucial for addressing congenital heart diseases and cardiomyopathies.
Purpose of the Study:
- To model human heart field development using human pluripotent stem cells (hPSCs).
- To delineate lineage specification and progression during human cardiogenesis.
- To identify distinct human cardiac mesoderm subpopulations and generate specific cardiomyocyte subtypes.
Main Methods:
- Utilized single-cell RNA-sequencing to analyze hPSC-derived and mouse mesoderm transcriptomes.
- Identified distinct human FHF, aSHF, and pSHF mesoderm subpopulations.
- Manipulated signaling pathways based on transcriptomic data to generate specific myocyte populations.
Main Results:
- Successfully modeled human heart field development from hPSCs.
- Identified distinct human FHF, aSHF, and pSHF mesoderm subpopulations.
- Generated cardiomyocyte populations with molecular characteristics of key subtypes, recapitulating mouse developmental trajectories and demonstrating conserved cardiovascular programs.
Conclusions:
- Established a comprehensive landscape of human embryonic cardiogenesis.
- Provided a model system for studying congenital heart diseases and chamber-specific cardiomyopathies.
- Opened avenues for developing novel therapeutic strategies for cardiac conditions.
Abstract:
The cardiomyocyte (CM) subtypes in the mammalian heart derive from distinct lineages known as the first heart field (FHF), the anterior second heart field (aSHF), and the posterior second heart field (pSHF) lineages that are specified during gastrulation. We modeled human heart field development from human pluripotent stem cells (hPSCs) by using single-cell RNA-sequencing to delineate lineage specification and progression. Analyses of hPSC-derived and mouse mesoderm transcriptomes enabled the identification of distinct human FHF, aSHF, and pSHF mesoderm subpopulations. Through staged manipulation of signaling pathways identified from transcriptomics, we generated myocyte populations that display molecular characteristics of key CM subtypes. The developmental trajectory of the human cardiac lineages recapitulated that of the mouse, demonstrating conserved cardiovascular programs. These findings establish a comprehensive landscape of human embryonic cardiogenesis that provides access to a broad spectrum of cardiomyocytes for modeling congenital heart diseases and chamber-specific cardiomyopathies as well as for developing new therapies to treat them.
