Evidence map›Paper›PMID 27942595›Full record

ArticleJCI insight2016

Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis.

Yan Xu, Takako Mizuno, Anusha Sridharan, Yina Du, Minzhe Guo, Jie Tang, Kathryn A Wikenheiser-Brokamp, Anne-Karina T Perl, Vincent A Funari, Jason J Gokey and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 381 papers.

0numbers the graph read from it
0cells of the map it votes in
381citing papers in PubMed
35.4field-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

381 citing papers in PubMed, 597 citations in OpenAlex.

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

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

12 authors at 1 institution in 1 country.

Yan XuDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Takako MizunoDepartment of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
Anusha SridharanDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Yina DuDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Minzhe GuoDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Jie TangDepartment of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
Kathryn A Wikenheiser-BrokampDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Anne-Karina T PerlDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Vincent A FunariDepartment of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
Jason J GokeyDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Barry R StrippDepartment of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
Jeffrey A WhitsettDivision of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Cedars-Sinai Medical Center · US

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Role of Surfactant Proteins in Mediating Noninfectious Inflammatory and FibroproP01HL108793 · NHLBI · DUKE UNIVERSITY · PI STRIPP, BARRY R · 2012 to 2022
$21.3M
ROLE OF ANGPTL4, AN ANGIOGENIC MEDIATOR, IN ARTHRITISP30AR047363 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI FLICK, MATTHEW J. · 2001 to 2015
$9.2M
Tissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan · 2016 to 2026
$7.7M
Pulmonary Development and Disease Pathogenesis Training ProgramT32HL007752 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Francis Xavier McCormack, Anne-Karina Theresia Perl · 1994 to 2026
$6.3M
Lung Repair and Regeneration Consortium Administrative Coordinating CenterU01HL110967 · NHLBI · DUKE UNIVERSITY · PI PALMER, SCOTT M · 2012 to 2016
$6.2M
Transcriptional Programming of Asthma Related Pathology in Respiratory EpitheliaR01HL095580 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI WHITSETT, JEFFREY A · 2009 to 2017
$4.7M
"Lung MAP" Atlas Research CenterU01HL122642 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI POTTER, S. STEVEN, WHITSETT, JEFFREY A · 2014 to 2018
$3.9M
Airway Progenitor Cell Profileration and Differentiation During Lung RepairU01HL110964 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI STREETER, PHILIP R, WHITSETT, JEFFREY A · 2012 to 2016
$3.3M
Role of EMC3/TMEM111 in Alveolar Epithelial Cell FunctionR01HL136722 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI LIN, XINHUA, WHITSETT, JEFFREY A · 2017 to 2020
$2.1M
Interstitial resident fibroblasts direct alveolar epithelial differentiationR01HL131661 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI PERL, ANNE-KARINA THERESIA · 2017 to 2020
$1.9M
Matrix fibroblasts are required for alveolar homeostasis and regrowthR56HL123969 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI PERL, ANNE-KARINA THERESIA · 2015 to 2015
$390k
NHLBI NIH HHS P01 HL108793NHLBI NIH HHS R01 HL095580NHLBI NIH HHS R01 HL131661NHLBI NIH HHS R01 HL136722NHLBI NIH HHS R56 HL123969NHLBI NIH HHS T32 HL007752NHLBI NIH HHS U01 HL110964NHLBI NIH HHS U01 HL110967NHLBI NIH HHS U01 HL122642NIAMS NIH HHS P30 AR047363NIAMS NIH HHS P30 AR070549NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease characterized by airway remodeling, inflammation, alveolar destruction, and fibrosis. We utilized single-cell RNA sequencing (scRNA-seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of normal human lung epithelial cells defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis. In contrast, scRNA-seq of IPF cells identified 3 distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and an additional atypical transitional cell that contributes to pathological processes in IPF. Individual IPF cells frequently coexpressed alveolar type 1 (AT1), AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development. Pathway analysis predicted aberrant activation of canonical signaling via TGF-β, HIPPO/YAP, P53, WNT, and AKT/PI3K. Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells. scRNA-seq analyses identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF. The present study provides a rich data source to further explore lung health and disease.

Indexed as

Sequence Analysis, RNAEpithelial CellsGene Expression ProfilingGenetic MarkersHumansIdiopathic Pulmonary FibrosisLungSingle-Cell AnalysisTranscriptomeGenetic Markers

Identifiers

PMID27942595
PMCPMC5135277
OpenAlexW2560076216

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.