[PDF][PDF] Endothelial reprogramming by disturbed flow revealed by single-cell RNA and chromatin accessibility study

A Andueza, S Kumar, J Kim, DW Kang, HL Mumme… - Cell reports, 2020 - cell.com
Cell reports, 2020cell.com
Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial
cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA
sequencing (scRNA-seq) and scATAC-seq study using endothelial-enriched single cells
from the left-and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA)
using the mouse partial carotid ligation (PCL) model. We find eight EC clusters along with
immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways …
Summary
Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNA-seq) and scATAC-seq study using endothelial-enriched single cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation (PCL) model. We find eight EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways, and pseudotime reveal that ECs are highly heterogeneous and plastic. D-flow induces a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory cells, mesenchymal (EndMT) cells, hematopoietic stem cells, endothelial stem/progenitor cells, and an unexpected immune cell-like (EndICLT) phenotypes. While confirming KLF4/KLF2 as an s-flow-sensitive transcription factor binding site, we also find those sensitive to d-flow (RELA, AP1, STAT1, and TEAD1). D-flow reprograms ECs from atheroprotective to proatherogenic phenotypes, including EndMT and potentially EndICLT.
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