Evidence map›Paper›PMID 33823868›Full record

ArticleRespiratory research2021

Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD.

Xiuying Li, Guillaume Noell, Tracy Tabib, Alyssa D Gregory, Humberto E Trejo Bittar, Ravi Vats, Tomasz W Kaminski, John Sembrat, Mark E Snyder, Divay Chandra and 11 more

Open access · goldAbstract read
In one paragraph

Article in Respiratory research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% 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

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3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 2 institutions in 2 countries.

Xiuying LiDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Guillaume NoellCentro Investigación Biomedica en Red (CIBERES), Institut D'investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Tracy TabibDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Alyssa D GregoryDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Humberto E Trejo BittarDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Ravi VatsVascular Medicine Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Tomasz W KaminskiVascular Medicine Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
John SembratDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Mark E SnyderDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Divay ChandraDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Kong ChenDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Chunbin ZouDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Yingze ZhangDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Prithu SunddVascular Medicine Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
John F McDyerDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Frank SciurbaDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Mauricio RojasDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Robert LafyatisDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Steve D ShapiroDepartment of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Rosa Faner *Centro Investigación Biomedica en Red (CIBERES), Institut D'investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Toru Nyunoya *Department of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA. nyunoyat@upmc.edu.ORCID http://orcid.org/0000-0002-0688-4607
University of Pittsburgh · USCentro de Investigación Biomédica en Red de Enfermedades Respiratorias · ES

Funding

Pulmonary arteriole occlusion by platelet-neutrophil micro-emboli in Acute Chest SyndromeR01HL128297 · NHLBI · VERSITI WISCONSIN, INC. · PI SUNDD, PRITHU · 2015 to 2025
$5.4M
Mechanisms of platelet exosome-mediated acute chest syndrome in sickle cell diseaseR01HL141080 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEAL, MATTHEW D, NOVELLI, ENRICO M · 2019 to 2022
$3.1M
Mapping Age-Related Changes in the LungU01HL145550 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENOS, PANAGIOTIS V, FINKEL, TOREN · 2019 to 2022
$2.4M
Role of FBXO24 mediated ubiquitination of FoxP1 protein in the pathogenesis and treatment of COPDR01HL153400 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHANDRA, DIVAY · 2020 to 2024
$2.3M
Epigenetic Modulation in Septic ImmunosuppressionR01HL142997 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZOU, CHUNBIN · 2019 to 2022
$1.8M
Role of TACC2 in smoking-induced COPDR01HL149719 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NYUNOYA, TORU · 2020 to 2023
$1.6M
Epigenetic Regulation in Acute Lung InjuryR01HL125435 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZOU, CHUNBIN · 2015 to 2018
$1.5M
Targeting F-box protein 048 in acute lung injuryI01CX000105 · VA · VETERANS HEALTH ADMINISTRATION · PI NYUNOYA, TORU · 2009 to 2022
–
American Heart Association 19TPA34830061CSRD VA I01 CX000105Instituto de Salud Carlos III CP16/00039Instituto de Salud Carlos III PI17/00369NHLBI NIH HHS HL149719NHLBI NIH HHS R01 HL125435NHLBI NIH HHS R01 HL128297NHLBI NIH HHS R01 HL141080NHLBI NIH HHS R01 HL142997NHLBI NIH HHS R01 HL149719NHLBI NIH HHS R01 HL153400NHLBI NIH HHS U01 HL145550Office of Academic Affiliations, Department of Veterans Affairs CX000105
6 · The paper itself

Abstract

backgroundWhole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified.

methodsTo determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed. Gene set enrichment analysis (GSEA) was used to identify the specific cell types contributing to the previously reported transcriptomic signatures.

resultsT-distributed stochastic neighbor embedding and clustering of scRNA seq data revealed a total of 17 distinct populations. Among them, the populations with more differentially expressed genes in cases vs. controls (log fold change >|0.4| and FDR = 0.05) were: monocytes (n = 1499); macrophages (n = 868) and ciliated epithelial cells (n = 590), respectively. Using GSEA, we found that only ciliated and cytotoxic T cells manifested a trend towards enrichment of the previously reported 127 regional emphysema gene signatures (normalized enrichment score [NES] = 1.28 and = 1.33, FDR = 0.085 and = 0.092 respectively). Among the significantly altered genes present in ciliated epithelial cells of the COPD lungs, QKI and IGFBP5 protein levels were also found to be altered in the COPD lungs.

conclusionsscRNA seq is useful for identifying transcriptional changes and possibly individual protein levels that may contribute to the development of emphysema in a cell-type specific manner.

Indexed as

AdultAgedEpithelial CellsFemaleGene Expression ProfilingHumansInsulin-Like Growth Factor Binding Protein 5LungMaleMiddle AgedPulmonary Disease, Chronic ObstructiveRNARNA-Binding ProteinsSequence Analysis, RNASeverity of Illness IndexTranscriptomeIGFBP5 protein, humanInsulin-Like Growth Factor Binding Protein 5QKI protein, humanRNARNA-Binding ProteinsCigarette smokeCOPDSingle cell RNA-seq

Identifiers

PMID33823868
PMCPMC8022543
OpenAlexW3145710320

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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.