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Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study
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 arter...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801938/ https://www.ncbi.nlm.nih.gov/pubmed/33326796 http://dx.doi.org/10.1016/j.celrep.2020.108491 |
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author | Andueza, Aitor Kumar, Sandeep Kim, Juyoung Kang, Dong-Won Mumme, Hope L. Perez, Julian I. Villa-Roel, Nicolas Jo, Hanjoong |
author_facet | Andueza, Aitor Kumar, Sandeep Kim, Juyoung Kang, Dong-Won Mumme, Hope L. Perez, Julian I. Villa-Roel, Nicolas Jo, Hanjoong |
author_sort | Andueza, Aitor |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7801938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-78019382021-01-12 Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study Andueza, Aitor Kumar, Sandeep Kim, Juyoung Kang, Dong-Won Mumme, Hope L. Perez, Julian I. Villa-Roel, Nicolas Jo, Hanjoong Cell Rep Article 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. 2020-12-15 /pmc/articles/PMC7801938/ /pubmed/33326796 http://dx.doi.org/10.1016/j.celrep.2020.108491 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Andueza, Aitor Kumar, Sandeep Kim, Juyoung Kang, Dong-Won Mumme, Hope L. Perez, Julian I. Villa-Roel, Nicolas Jo, Hanjoong Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study |
title | Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study |
title_full | Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study |
title_fullStr | Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study |
title_full_unstemmed | Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study |
title_short | Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study |
title_sort | endothelial reprogramming by disturbed flow revealed by single-cell rna and chromatin accessibility study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801938/ https://www.ncbi.nlm.nih.gov/pubmed/33326796 http://dx.doi.org/10.1016/j.celrep.2020.108491 |
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