Characterizing the behavior of coronary endothelial cells in the mouse heart after injury and during neonatal development

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Coronary artery disease (CAD) compromises the heart muscle’s essential blood supply and remains the leading cause of death worldwide. Surgical interventions to restore blood flow are too invasive for many CAD patients. Studying how the coronary vasculature develops and responds to injury may inform new therapies based on stimulating artery growth and regeneration. Coronary endothelial cells (ECs) derive from multiple progenitor sources, yet it remains unknown whether their developmental lineage affects their response to injury in the adult heart. By modeling cardiac injury in adult mice and quantifying lineage-labeled proliferating ECs, we discovered that lineage did not influence response to injury with respect to proliferation. Proliferating ECs were observed in arteries, suggesting that injury can induce arteries to re-enter the cell cycle at adult stages. During neonatal development, injury induces more substantial artery proliferation which enables the neonatal mouse heart to revascularize and regenerate damaged tissue. Using single-cell RNA sequencing, this study explores transcriptional properties in artery ECs that may support neonatal regeneration. Based on the analysis of differentially expressed genes between early and late neonatal stages, we present a list of candidate genes regulating artery regeneration. Unexpectedly, we also identified a population of artery cells that retain cell fate plasticity and switch to a capillary fate during neonatal development. Our findings contribute to a more complete understanding of EC behaviors in the postnatal heart and may inform future therapies to achieve artery regeneration and mitigate CAD mortality.


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Date created June 2021


Author Krieger, Josephine Elise
Primary advisor Red-Horse, Kristy
Advisor McConnell, Susan
Degree granting institution Stanford University, Department of Biology, 2021


Subject Biology
Subject developmental biology
Subject coronary artery disease
Subject vascular endothelial cells
Subject neonatal regeneration
Genre Thesis

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This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).

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Krieger, Josephine Elise and Red-Horse, Kristy and McConnell, Susan. (2021). Characterizing the behavior of coronary endothelial cells in the mouse heart after injury and during neonatal development. Stanford Digital Repository. Available at:


Undergraduate Theses, Department of Biology, 2020-2021

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