Single-Cell RNA Sequencing Reveals Endothelial Cell Transcriptome Heterogeneity Under Homeostatic Laminar Flow. Arterioscler Thromb Vasc Biol 2021 Oct;41(10):2575-2584
Date
08/27/2021Pubmed ID
34433297Pubmed Central ID
PMC8454496DOI
10.1161/ATVBAHA.121.316797Scopus ID
2-s2.0-85116134582 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Objective: Endothelial cells (ECs) that form the innermost layer of all vessels exhibit heterogeneous cell behaviors and responses to pro-angiogenic signals that are critical for vascular sprouting and angiogenesis. Once vessels form, remodeling and blood flow lead to EC quiescence, and homogeneity in cell behaviors and signaling responses. These changes are important for the function of mature vessels, but whether and at what level ECs regulate overall expression heterogeneity during this transition is poorly understood. Here, we profiled EC transcriptomic heterogeneity, and expression heterogeneity of selected proteins, under homeostatic laminar flow. Approach and Results: Single-cell RNA sequencing and fluorescence microscopy were used to characterize heterogeneity in RNA and protein gene expression levels of human ECs under homeostatic laminar flow compared to nonflow conditions. Analysis of transcriptome variance, Gini coefficient, and coefficient of variation showed that more genes increased RNA heterogeneity under laminar flow relative to genes whose expression became more homogeneous, although small subsets of cells did not follow this pattern. Analysis of a subset of genes for relative protein expression revealed little congruence between RNA and protein heterogeneity changes under flow. In contrast, the magnitude of expression level changes in RNA and protein was more coordinated among ECs in flow versus nonflow conditions. Conclusions: ECs exposed to homeostatic laminar flow showed overall increased heterogeneity in RNA expression levels, while expression heterogeneity of selected cognate proteins did not follow RNA heterogeneity changes closely. These findings suggest that EC homeostasis is imposed post-transcriptionally in response to laminar flow.
Author List
Liu Z, Ruter DL, Quigley K, Tanke NT, Jiang Y, Bautch VLAuthor
Ziqing Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCells, Cultured
Gene Expression Profiling
Human Umbilical Vein Endothelial Cells
Humans
Mechanotransduction, Cellular
Mice
Microscopy, Fluorescence
Regional Blood Flow
Single-Cell Analysis
Stress, Mechanical
Transcriptome
