Related Experiment Video
Updated: Apr 27, 2026
Live Imaging of Early Cardiac Progenitors in the Mouse Embryo
Published on: July 12, 2022
SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development
Rhys J P Skelton1, Magdaline Costa2, David J Anderson1
1Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
Insights
Researchers mapped human heart development using cell markers like NKX2-5. This reveals distinct stages of cardiomyocyte and endothelial cell differentiation, creating a foundation for a human cardiogenesis fate map.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Cardiovascular Research
Background:
- Establishing a detailed cell lineage fate map for human cardiogenesis is crucial for understanding heart development.
- Existing maps for other lineages highlight the need for similar detailed studies in cardiovascular development.
Purpose of the Study:
- To define cell lineage relationships during human cardiovascular development.
- To identify specific cell surface markers and transcription factors that delineate distinct stages of cardiac progenitor and cardiomyocyte differentiation.
Main Methods:
- Utilized NKX2-5(GFP) human embryonic stem cells (hESCs) to track cardiac progenitors and cardiomyocytes.
- Sub-fractionated cardiovascular cell lineages based on SIRPA, VCAM1, and CD34 expression.
- Assayed differentiation potential and gene expression of isolated cell populations.
Main Results:
- Identified NKX2-5(pos)CD34(pos) cells as precursors to endothelial cells, which downregulate NKX2-5.
- Demonstrated that myocardial committed cells maintain NKX2-5 expression, progressing through SIRPA and VCAM1 expression stages.
- Observed VCAM1 upregulation correlated with myofilament marker expression and reduced cell potential, indicating lineage restriction.
Conclusions:
- Combinatorial expression of NKX2-5, SIRPA, VCAM1, and CD34 defines discrete stages of cardiovascular cell differentiation.
- These markers provide a framework for a human cardiogenesis fate map, identifying specific stages of cardiomyocyte and endothelial lineage commitment.
Abstract:
The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5(GFP) was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5(GFP/w) human embryonic stem cells (hESCs). Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5(pos)CD34(pos) population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5(pos)SIRPA(pos) to NKX2-5(pos)SIRPA(pos)VCAM1(pos). Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.
