Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Andueza, Aitor, Kumar, Sandeep, Kim, Juyoung, Kang, Dong-Won, Mumme, Hope L., Perez, Julian I., Villa-Roel, Nicolas, Jo, Hanjoong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
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
_version_ 1783635679076417536
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
work_keys_str_mv AT anduezaaitor endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT kumarsandeep endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT kimjuyoung endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT kangdongwon endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT mummehopel endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT perezjuliani endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT villaroelnicolas endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy
AT johanjoong endothelialreprogrammingbydisturbedflowrevealedbysinglecellrnaandchromatinaccessibilitystudy