Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension

Abstract Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diver...

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Autores principales:	Kewal Asosingh, Suzy Comhair, Lori Mavrakis, Weiling Xu, Dean Horton, Ian Taylor, Svyatoslav Tkachenko, Bo Hu, Serpil Erzurum
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5957dda4c4c64cda823596cd73771ffd
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spelling	oai:doaj.org-article:5957dda4c4c64cda823596cd73771ffd2021-12-02T17:55:13ZSingle-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension10.1038/s41598-021-94163-y2045-2322https://doaj.org/article/5957dda4c4c64cda823596cd73771ffd2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94163-yhttps://doaj.org/toc/2045-2322Abstract Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diversity among endothelial cells in the healthy pulmonary vascular bed and the pathologic diversity among pulmonary arterial endothelial cells (PAEC) in PAH is unknown and previously unexplored. Here single-cell RNA sequencing technology was used to decipher the cellular heterogeneity among PAEC in the human pulmonary arteries isolated from explanted lungs from three patients with PAH undergoing lung transplantation and three healthy donor lungs not utilized for transplantation. Datasets of 36,368 PAH individual endothelial cells and 36,086 healthy cells were analyzed using the SeqGeq bioinformatics program. Total population differential gene expression analyses identified 629 differentially expressed genes between PAH and controls. Gene Ontology and Canonical Ingenuity analysis revealed pathways that are known to be involved in pathogenesis, as well as unique new pathways. At the individual cell level, dimensionality reduction followed by density based clustering revealed the presence of eight unique PAEC clusters that were typified by proliferative, angiogenic or quiescent phenotypes. While control and PAH harbored many similar subgroups of endothelial cells, PAH had greater proportions of angiogenic and proliferative subsets. These findings identify that only specific subgroups of PAH PAEC have gene expression different than healthy PAEC, and suggest these subpopulations lead to the pathologic functions leading to remodeling.Kewal AsosinghSuzy ComhairLori MavrakisWeiling XuDean HortonIan TaylorSvyatoslav TkachenkoBo HuSerpil ErzurumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kewal Asosingh Suzy Comhair Lori Mavrakis Weiling Xu Dean Horton Ian Taylor Svyatoslav Tkachenko Bo Hu Serpil Erzurum Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
description	Abstract Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diversity among endothelial cells in the healthy pulmonary vascular bed and the pathologic diversity among pulmonary arterial endothelial cells (PAEC) in PAH is unknown and previously unexplored. Here single-cell RNA sequencing technology was used to decipher the cellular heterogeneity among PAEC in the human pulmonary arteries isolated from explanted lungs from three patients with PAH undergoing lung transplantation and three healthy donor lungs not utilized for transplantation. Datasets of 36,368 PAH individual endothelial cells and 36,086 healthy cells were analyzed using the SeqGeq bioinformatics program. Total population differential gene expression analyses identified 629 differentially expressed genes between PAH and controls. Gene Ontology and Canonical Ingenuity analysis revealed pathways that are known to be involved in pathogenesis, as well as unique new pathways. At the individual cell level, dimensionality reduction followed by density based clustering revealed the presence of eight unique PAEC clusters that were typified by proliferative, angiogenic or quiescent phenotypes. While control and PAH harbored many similar subgroups of endothelial cells, PAH had greater proportions of angiogenic and proliferative subsets. These findings identify that only specific subgroups of PAH PAEC have gene expression different than healthy PAEC, and suggest these subpopulations lead to the pathologic functions leading to remodeling.
format	article
author	Kewal Asosingh Suzy Comhair Lori Mavrakis Weiling Xu Dean Horton Ian Taylor Svyatoslav Tkachenko Bo Hu Serpil Erzurum
author_facet	Kewal Asosingh Suzy Comhair Lori Mavrakis Weiling Xu Dean Horton Ian Taylor Svyatoslav Tkachenko Bo Hu Serpil Erzurum
author_sort	Kewal Asosingh
title	Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
title_short	Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
title_full	Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
title_fullStr	Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
title_full_unstemmed	Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
title_sort	single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5957dda4c4c64cda823596cd73771ffd
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Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension

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