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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Crnkovic, S; Valzano, F; Fließer, E; Gindlhuber, J; Thekkekara, Puthenparampil, H; Basil, M; Morley, MP; Katzen, J; Gschwandtner, E; Klepetko, W; Cantu, E; Wolinski, H; Olschewski, H; Lindenmann, J; Zhao, YY; Morrisey, EE; Marsh, LM; Kwapiszewska, G.
Single-cell transcriptomics reveals skewed cellular communication and phenotypic shift in pulmonary artery remodeling.
JCI Insight. 2022; 7(20): Doi: 10.1172/jci.insight.153471 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Crnkovic Slaven
Kwapiszewska-Marsh Grazyna
Valzano Francesco
Co-Autor*innen der Med Uni Graz
Fließer Elisabeth
Gindlhuber Jürgen
Gschwandtner Elisabeth
Lindenmann Jörg
Marsh Leigh
Olschewski Horst
Thekkekara Puthenparampil Helene
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Mice - administration & dosage
Humans - administration & dosage
Animals - administration & dosage
Vascular Remodeling - genetics
Muscle, Smooth, Vascular - administration & dosage
Pulmonary Artery - pathology
Transcriptome - administration & dosage
Oxygen - administration & dosage

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