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Updated: May 16, 2025
Derivation of Cardiac Progenitor Cells from Embryonic Stem Cells
Published on: January 12, 2015
HAND1 level controls the specification of multipotent cardiac and extraembryonic progenitors from human pluripotent
Adam T Lynch1, Naomi Phillips1, Megan Douglas1
1Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Insights
Researchers identified the transcription factor HAND1
Area of Science:
- Developmental biology
- Stem cell research
- Genetics
Background:
- Mechanisms of embryonic heart development are not fully understood.
- Diverse progenitor cells contribute to cardiac formation.
- Human pluripotent stem cells (hPSCs) offer a model for studying early development.
Purpose of the Study:
- To decipher cardiac and non-cardiac lineage trajectories during hPSC differentiation.
- To identify key transcription factors regulating cell specification, identity, and function.
- To understand the role of HAND1 in mesodermal progenitor fate determination.
Main Methods:
- Utilized a human pluripotent stem cell (hPSC) model.
- Analyzed differentiation pathways and lineage trajectories.
- Investigated the gene regulatory network of HAND1.
Main Results:
- Discovered a concentration-dependent function for HAND1 in mesodermal progenitors.
- Low HAND1 levels promote multipotent juxta-cardiac field progenitors (cardiomyocytes, epicardial cells).
- High HAND1 levels promote extraembryonic mesoderm development; HAND1-low progenitors can be propagated.
Conclusions:
- HAND1 acts as a crucial fate determinant in early cardiac development.
- Mechanistic insights into HAND1 function can advance disease modeling for congenital heart disease.
- This study provides a foundation for cell therapy and regenerative medicine approaches.
Abstract:
Diverse sets of progenitors contribute to the development of the embryonic heart, but the mechanisms of their specification have remained elusive. Here, using a human pluripotent stem cell (hPSC) model, we deciphered cardiac and non-cardiac lineage trajectories in differentiation and identified transcription factors underpinning cell specification, identity and function. We discovered a concentration-dependent, fate determining function for the basic helix-loop-helix transcription factor HAND1 in mesodermal progenitors and uncovered its gene regulatory network. At low expression level, HAND1 directs differentiation towards multipotent juxta-cardiac field progenitors able to make cardiomyocytes and epicardial cells, whereas at high level it promotes the development of extraembryonic mesoderm. Importantly, HAND1-low progenitors can be propagated in their multipotent state. This detailed mechanistic insight into human development has the potential to accelerate the delivery of effective disease modelling, including for congenital heart disease, and cell therapy-based regenerative medicine.
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