Single-cell transcriptomics reveals skewed cellular communication and phenotypic shift in pulmonary artery remodeling.

Autor:	Crnkovic S; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.; Division of Physiology & Pathophysiology, Otto Loewi Research Center and., Valzano F; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria., Fließer E; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria., Gindlhuber J; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.; Diagnostic and Research Institute of Pathology, Diagnostic and Research Center of Molecular BioMedicine, Medical University of Graz, Graz, Austria., Thekkekara Puthenparampil H; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria., Basil M; Penn Center for Pulmonary Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Morley MP; Penn Center for Pulmonary Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Katzen J; Penn Center for Pulmonary Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Gschwandtner E; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Klepetko W; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Cantu E; Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Wolinski H; Institute of Molecular Biosciences and.; Field of Excellence BioHealth, University of Graz, Graz, Austria., Olschewski H; Division of Pulmonology, Department of Internal Medicine; and., Lindenmann J; Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria., Zhao YY; Program for Lung and Vascular Biology, Section of Injury Repair and Regeneration, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.; Departments of Pediatrics, Pharmacology, and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, USA., Morrisey EE; Penn Center for Pulmonary Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Marsh LM; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.; Division of Physiology & Pathophysiology, Otto Loewi Research Center and., Kwapiszewska G; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.; Division of Physiology & Pathophysiology, Otto Loewi Research Center and.; Institute of Lung Health, German Center for Lung Research (DZL), Giessen, Germany.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2022 Oct 24; Vol. 7 (20). Date of Electronic Publication: 2022 Oct 24.
DOI:	10.1172/jci.insight.153471
Abstrakt:	A central feature of progressive vascular remodeling is altered smooth muscle cell (SMC) homeostasis; however, the understanding of how different cell populations contribute to this process is limited. Here, we utilized single-cell RNA sequencing to provide insight into cellular composition changes within isolated pulmonary arteries (PAs) from pulmonary arterial hypertension and donor lungs. Our results revealed that remodeling skewed the balanced communication network between immune and structural cells, in particular SMCs. Comparative analysis with murine PAs showed that human PAs harbored heterogeneous SMC populations with an abundant intermediary cluster displaying a gradient transition between SMCs and adventitial fibroblasts. Transcriptionally distinct SMC populations were enriched in specific biological processes and could be differentiated into 4 major clusters: oxygen sensing (enriched in pericytes), contractile, synthetic, and fibroblast-like. End-stage remodeling was associated with phenotypic shift of preexisting SMC populations and accumulation of synthetic SMCs in neointima. Distinctly regulated genes in clusters built nonredundant regulatory hubs encompassing stress response and differentiation regulators. The current study provides a blueprint of cellular and molecular changes on a single-cell level that are defining the pathological vascular remodeling process.
Databáze:	MEDLINE
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