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Updated: Jan 23, 2026
Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial
Ziwen Li1, Emmanouil G Solomonidis1, Marco Meloni1
1Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Aims:
A better understanding of the pathways that regulate regeneration of the coronary vasculature is of fundamental importance for the advancement of strategies to treat patients with heart disease. Here, we aimed to investigate the origin and clonal dynamics of endothelial cells (ECs) associated with neovascularization in the adult mouse heart following myocardial infarction (MI). Furthermore, we sought to define murine cardiac endothelial heterogeneity and to characterize the transcriptional profiles of pro-angiogenic resident ECs in the adult mouse heart, at single-cell resolution.
Methods And Results:
An EC-specific multispectral lineage-tracing mouse (Pdgfb-iCreERT2-R26R-Brainbow2.1) was used to demonstrate that structural integrity of adult cardiac endothelium following MI was maintained through clonal proliferation by resident ECs in the infarct border region, without significant contributions from bone marrow cells or endothelial-to-mesenchymal transition. Ten transcriptionally discrete heterogeneous EC states, as well as the pathways through which each endothelial state is likely to enhance neovasculogenesis and tissue regeneration following ischaemic injury were defined. Plasmalemma vesicle-associated protein (Plvap) was selected for further study, which showed an endothelial-specific and increased expression in both the ischaemic mouse and human heart, and played a direct role in regulating human endothelial proliferation in vitro.
Conclusion:
We present a single-cell gene expression atlas of cardiac specific resident ECs, and the transcriptional hierarchy underpinning endogenous vascular repair following MI. These data provide a rich resource that could assist in the development of new therapeutic interventions to augment endogenous myocardial perfusion and enhance regeneration in the injured heart.
Insights
Adult heart endothelial cells (ECs) regenerate after myocardial infarction (MI) via resident EC proliferation. This study defines EC heterogeneity and transcriptional profiles, identifying Plvap as crucial for endothelial proliferation and cardiac repair.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Single-cell Genomics
Background:
- Understanding coronary vasculature regeneration is crucial for treating heart disease.
- Myocardial infarction (MI) triggers complex vascular repair processes.
- Endothelial cell (EC) heterogeneity and function in cardiac repair remain incompletely understood.
Purpose of the Study:
- Investigate the origin and clonal dynamics of ECs in adult mouse heart neovascularization post-MI.
- Define cardiac endothelial heterogeneity at single-cell resolution.
- Characterize transcriptional profiles of pro-angiogenic resident ECs.
Main Methods:
- Utilized an EC-specific lineage-tracing mouse model (Pdgfb-iCreERT2-R26R-Brainbow2.1).
- Performed single-cell RNA sequencing to define EC transcriptional states.
- Investigated the role of Plasmalemma vesicle-associated protein (Plvap) in EC proliferation.
Main Results:
- Adult cardiac endothelium integrity post-MI is maintained by resident EC clonal proliferation in the infarct border zone.
- Identified ten transcriptionally distinct EC states and their roles in neovascularization.
- Plvap expression is upregulated in ischemic hearts (mouse and human) and directly promotes human EC proliferation in vitro.
Conclusions:
- Generated a single-cell gene expression atlas of cardiac resident ECs, revealing the transcriptional hierarchy of vascular repair post-MI.
- These findings offer a valuable resource for developing therapies to enhance myocardial perfusion and regeneration.
- The study highlights the importance of resident ECs and specific factors like Plvap in cardiac repair.
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