Evidence map›Paper›PMID 39484590›Full record

ArticlebioRxiv : the preprint server for biology2024

Single-cell transcriptomics reveal diverging pathobiology and opportunities for precision targeting in scleroderma-associated versus idiopathic pulmonary arterial hypertension.

Tijana Tuhy, Julie C Coursen, Tammy Graves, Michael Patatanian, Christopher Cherry, Shannon E Niedermeyer, Sarah L Khan, Darin T Rosen, Michael P Croglio, Mohab Elnashar and 8 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Tijana TuhyDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-8922-9471
Julie C CoursenDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Tammy GravesDivision of Pulmonary Medicine, Indiana University, Indianapolis, IN, USA.
Michael PatatanianDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Christopher CherryDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Shannon E NiedermeyerDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sarah L KhanDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Darin T RosenDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0001-5352-9288
Michael P CroglioDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Mohab ElnasharFaculty of Medicine, Ain Shams University, Cairo, Egypt.
Todd M KolbDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Stephen C MathaiDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Rachel L DamicoDivision of Pulmonary and Critical Care Medicine, University of Miami, Miami, FL, USA.
Paul M HassounDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-0601-4975
Larissa A ShimodaDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Karthik SureshDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-2920-0949
Micheala A AldredDivision of Pulmonary Medicine, Indiana University, Indianapolis, IN, USA.
Catherine E SimpsonDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

Funding

MULTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASEST32HL007534 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Nadia N Hansel, Larissa A. Shimoda · 1985 to 2026
$28.3M
Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
The role of xanthine oxidoreductase activity and altered metabolism in scleroderma-associated pulmonary arterial hypertensionK23HL153781 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SIMPSON, CATHERINE · 2020 to 2024
$883k
NHLBI NIH HHS K23 HL153781NHLBI NIH HHS R24 HL123767NHLBI NIH HHS T32 HL007534
6 · The paper itself

Abstract

Introduction: Pulmonary arterial hypertension (PAH) involves progressive cellular and molecular change within the pulmonary vasculature, leading to increased vascular resistance. Current therapies targeting nitric oxide (NO), endothelin, and prostacyclin pathways yield variable treatment responses. Patients with systemic sclerosis-associated PAH (SSc-PAH) often experience worse outcomes than those with idiopathic PAH (IPAH). Methods: Lung tissue samples from four SSc-PAH, four IPAH, and four failed donor specimens were obtained from the Pulmonary Hypertension Breakthrough Initiative (PHBI) lung tissue bank. Single-cell RNA sequencing (scRNAseq) was performed using the 10X Genomics Chromium Flex platform. Data normalization, clustering, and differential expression analysis were conducted using Seurat. Additional analyses included gene set enrichment analysis (GSEA), transcription factor activity analysis, and ligand-receptor signaling. Pharmacotranscriptomic screening was performed using the Connectivity Map. Results: SSc-PAH samples showed a higher proportion of fibroblasts and dendritic cells/macrophages compared to IPAH and donor samples. GSEA revealed enriched pathways related to epithelial-to-mesenchymal transition (EMT), apoptosis, and vascular remodeling in SSc-PAH samples. There was pronounced differential gene expression across diverse pulmonary vascular cell types and in various epithelial cell types in both IPAH and SSc-PAH, with epithelial to endothelial cell signaling observed. Macrophage to endothelial cell signaling was particularly pronounced in SSc-PAH. Pharmacotranscriptomic screening identified TIE2, GSK-3, and PKC inhibitors, among other compounds, as potential drug candidates for reversing SSc-PAH gene expression signatures. Discussion: Overlapping and distinct gene expression patterns exist in SSc-PAH versus IPAH, with significant molecular differences suggesting unique pathogenic mechanisms in SSc-PAH. These findings highlight the potential for precision-targeted therapies to improve SSc-PAH patient outcomes. Future studies should validate these targets clinically and explore their therapeutic efficacy.

Identifiers

PMID39484590
PMCPMC11527343

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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 OpenQuestion graph.