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Updated: May 28, 2026
Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
Vascular endothelial and endocardial progenitors differentiate as cardiomyocytes in the absence of Etsrp/Etv2
Sharina Palencia-Desai1, Vikram Kohli, Jione Kang
1Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Insights
The ETS transcription factor Etv2 (also known as Etsrp) is essential for cardiovascular development. In zebrafish, Etsrp promotes endothelial and endocardial cell fates while inhibiting cardiomyocyte differentiation, revealing distinct mechanisms for lineage specification.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Cardiovascular Research
Background:
- Multipotent cardiovascular progenitors are hypothesized to give rise to vascular endothelial, endocardial, and myocardial lineages.
- The in vivo existence of these progenitors and the molecular regulation of cardiovascular lineage specification remain poorly understood.
- Etv2 (Etsrp/ER71), an ETS domain transcription factor, is a known regulator of vascular endothelial differentiation.
Purpose of the Study:
- To investigate the role of Etsrp in cardiovascular lineage specification during zebrafish embryonic development.
- To elucidate the molecular mechanisms by which Etsrp regulates endothelial, endocardial, and myocardial differentiation.
- To understand the interplay between Etsrp and Foxc1a in endocardial development and myocardial inhibition.
Main Methods:
- Utilized zebrafish knockdown and mutant models to assess Etsrp function.
- Analyzed the expression of specific endothelial, endocardial, and myocardial markers (e.g., nfatc1, hand2, cmlc2).
- Investigated the regulatory relationship between Etsrp, Foxc1a, and target gene expression.
Main Results:
- Etsrp deficiency leads to the differentiation of etsrp-expressing progenitors into cardiomyocytes, with reduced endocardial marker expression.
- Etsrp directly induces endocardial nfatc1 expression and inhibits myocardial differentiation by preventing hand2 and cmlc2 expression.
- Foxc1a is crucial for initiating endocardial development and interacts with Etsrp, but is not required for inhibiting myocardial differentiation.
Conclusions:
- Etsrp plays a dual role in cardiovascular development: initiating endothelial/endocardial fates and inhibiting myocardial differentiation via distinct mechanisms.
- These findings clarify genetic pathways controlling cardiovascular differentiation in vertebrates.
- The study provides insights relevant to stem cell research for cardiac tissue regeneration.
Abstract:
Previous studies have suggested that embryonic vascular endothelial, endocardial and myocardial lineages originate from multipotential cardiovascular progenitors. However, their existence in vivo has been debated and molecular mechanisms that regulate specification of different cardiovascular lineages are poorly understood. An ETS domain transcription factor Etv2/Etsrp/ER71 has been recently established as a crucial regulator of vascular endothelial differentiation in zebrafish and mouse embryos. In this study, we show that etsrp-expressing vascular endothelial/endocardial progenitors differentiate as cardiomyocytes in the absence of Etsrp function during zebrafish embryonic development. Expression of multiple endocardial specific markers is absent or greatly reduced in Etsrp knockdown or mutant embryos. We show that Etsrp regulates endocardial differentiation by directly inducing endocardial nfatc1 expression. In addition, Etsrp function is required to inhibit myocardial differentiation. In the absence of Etsrp function, etsrp-expressing endothelial and endocardial progenitors initiate myocardial marker hand2 and cmlc2 expression. Furthermore, Foxc1a function and interaction between Foxc1a and Etsrp is required to initiate endocardial development, but is dispensable for the inhibition of myocardial differentiation. These results argue that Etsrp initiates endothelial and endocardial, and inhibits myocardial, differentiation by two distinct mechanisms. Our findings are important for the understanding of genetic pathways that control cardiovascular differentiation during normal vertebrate development and will also greatly contribute to the stem cell research aimed at regenerating heart tissues.
