Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study
| Autor: | Hope L. Mumme, Julian I. Perez, Hanjoong Jo, Nicolas Villa-Roel, Sandeep Kumar, Juyoung Kim, Dong Won Kang, Aitor Andueza |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endothelium Endothelium single-cell RNA sequencing General Biochemistry Genetics and Molecular Biology Article single-cell ATAC sequencing 03 medical and health sciences Mice 0302 clinical medicine medicine blood flow Animals Humans Progenitor cell lcsh:QH301-705.5 Chemistry reprogramming Endothelial Cells Cellular Reprogramming Chromatin endothelial-to-mesenchymal transition Cell biology Haematopoiesis 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) KLF4 KLF2 RNA Stem cell Reprogramming 030217 neurology & neurosurgery |
| Zdroj: | Cell reports Cell Reports, Vol 33, Iss 11, Pp 108491-(2020) |
| ISSN: | 2211-1247 |
| Popis: | 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. Graphical Abstract In Brief To determine the effect of proatherogenic disturbed flow on transcriptomic and epigenomic chromatin accessibility profiles in endothelial cells at single-cell resolution, Andueza et al. perform scRNA-seq and scATAC-seq analyses using mouse carotid arteries following the partial carotid ligation. Disturbed flow reprograms endothelial cells to proatherogenic phenotypes, including EndMT and endothelial-to-immune cell-like transition. |
| Databáze: | OpenAIRE |
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