Evidence map›Paper›PMID 34528097›Full record

ArticleCardiovascular research2022

Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension.

Julie Rodor, Shiau Haln Chen, Jessica P Scanlon, João P Monteiro, Axelle Caudrillier, Sweta Sweta, Katherine Ross Stewart, Alena Shmakova, Ross Dobie, Beth E P Henderson and 16 more

Open access · hybridAbstract read
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 2 pooled it
13.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Interpreting Pulmonary Hypertension Beyond Single Cells.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  5. CD157Stem cell reports · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. RareInnovation (Cambridge (Mass.)) · 2026
    Article
  15. Review
  16. Review
  17. Article
  18. Endothelial Heterogeneity in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  19. Article
  20. Article

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 3 countries.

Julie RodorCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0003-2900-5780
Shiau Haln ChenCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0001-9947-4668
Jessica P ScanlonCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-4792-7079
João P MonteiroCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0001-6481-6875
Axelle CaudrillierCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Sweta SwetaCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Katherine Ross StewartCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-0760-0514
Alena ShmakovaCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Ross DobieCentre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0001-9516-315X
Beth E P HendersonCentre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Kevin StewartCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0003-4579-6826
Patrick W F HadokeCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-1041-1781
Mark SouthwoodDepartment of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0002-3493-9599
Stephen D MooreDepartment of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Paul D UptonDepartment of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0003-2716-4921
Nick W MorrellDepartment of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0001-5700-9792
Ziwen LiCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-1668-0229
Stephen Y ChanDivisions of Cardiology and Rheumatology, Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-9520-7527
Adam HandenDivisions of Cardiology and Rheumatology, Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-1371-9466
Robert LafyatisDivisions of Cardiology and Rheumatology, Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-9398-5034
Laura P M H de RooijLaboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, Center for Cancer Biology, Leuven Cancer Institute (LKI), VIB and KU Leuven, Leuven 3000, Belgium.ORCID 0000-0002-1810-4620
Neil C HendersonCentre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-2273-4094
Peter CarmelietLaboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, Center for Cancer Biology, Leuven Cancer Institute (LKI), VIB and KU Leuven, Leuven 3000, Belgium.ORCID 0000-0001-7961-1821
Ana Mishel SpiroskiCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-8584-8048
Mairi BrittanCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0002-3830-200X
Andrew H BakerCentre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.ORCID 0000-0003-1441-5576
The Queen's Medical Research Institute · GBUniversity of Cambridge · GBCentre for Inflammation Research · GBUniversity of Pittsburgh Medical Center · USVIB-KU Leuven Center for Cancer Biology · BE

Funding

Defining the Complex Biology of the miR-130/301 Family in Pulmonary HypertensionR01HL124021 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y · 2014 to 2025
$4.9M
Iron-Sulfur Deficiency as a Critical Pathogenic Cause of Pulmonary HypertensionR01HL122596 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y · 2015 to 2024
$4.5M
Molecular Drivers of Vascular Stiffness and Metabolic Dysfunction in HIV-Induced Pulmonary Arterial HypertensionR01HL138437 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y, NORRIS, KAREN A · 2017 to 2020
$2.4M
British Heart Foundation CH/09/001/25945British Heart Foundation CH/11/2/28733British Heart Foundation RE/18/5/34216British Heart Foundation RG/13/4/30107British Heart Foundation RG/14/3/30706British Heart Foundation RG/19/3/34265British Heart Foundation RG/20/5/34796NHLBI NIH HHS R01 HL122596NHLBI NIH HHS R01 HL124021NHLBI NIH HHS R01 HL138437Wellcome Trust
6 · The paper itself

Abstract

aimsEndothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution. METHODS AND

resultsWe carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility, and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and microvasculature.

conclusionThis study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development.

Indexed as

Hypertension, PulmonaryPulmonary Arterial HypertensionAnimalsEndothelial CellsFamilial Primary Pulmonary HypertensionHumansMicePulmonary ArteryRatsSequence Analysis, RNAEndothelial cellsPAHPulmonary hypertensionSingle-cell RNA-seq

Identifiers

PMID34528097
PMCPMC9400412
OpenAlexW3199380250

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.