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Related Experiment Video

Updated: Nov 2, 2025

Isolation and Profiling of Human Primary Mesenteric Arterial Endothelial Cells at the Transcriptome Level
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Single-Cell Transcriptomics Reveals Endothelial Plasticity During Diabetic Atherogenesis.

Guizhen Zhao1, Haocheng Lu1, Yuhao Liu1,2

  • 1Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, United States.

Frontiers in Cell and Developmental Biology
|June 7, 2021
PubMed
Summary

Diabetic atherosclerosis alters endothelial cells (ECs), causing dysfunction. Our study reveals EC heterogeneity and plasticity, with a key transition to fibroblast-like cells impacting disease progression.

Keywords:
atherosclerosisdiabetesendothelial cellsingle-cell RNA-sequencingtranscriptomic heterogeneity

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Area of Science:

  • Cardiovascular Biology
  • Metabolic Disease Research
  • Single-Cell Genomics

Background:

  • Atherosclerosis is a primary cause of cardiovascular disease and mortality in diabetic patients.
  • Endothelial cell (EC) dysfunction is an early, critical step in atherosclerosis, exacerbated by diabetes.
  • Transcriptomic changes in ECs during diabetic atherosclerosis are not well understood.

Purpose of the Study:

  • To investigate the transcriptomic heterogeneity of endothelial cells in diabetic atherosclerosis.
  • To explore endothelial cell plasticity and identify cell states in response to a diabetogenic diet.
  • To characterize metabolic changes in endothelial cells during diabetes-associated atherogenesis.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) of EC-enriched cells from mouse heart and aorta.
  • Dietary intervention with a standard chow or a diabetogenic high-fat diet with cholesterol for 12 weeks.
  • Analysis of EC clusters, marker genes, pathways, and metabolic functions.

Main Results:

  • Identified eight distinct EC clusters, with three showing mesenchymal markers indicating endothelial-to-mesenchymal transition (EndMT).
  • Demonstrated significant EC heterogeneity and plasticity in both normal and atherosclerotic conditions.
  • EndMT-derived fibroblast-like cells are prevalent in atherosclerosis, exhibiting reduced fatty acid oxidation and altered extracellular matrix regulation and apoptosis.

Conclusions:

  • Characterized the phenotypic and metabolic heterogeneity of endothelial cells in diabetes-associated atherogenesis at the single-cell level.
  • Highlighted the role of EndMT in diabetic atherosclerosis, leading to fibroblast-like cells with altered metabolic functions.
  • Provided insights into endothelial cell biology and cardiovascular disease mechanisms in diabetes.