Evidence map›Paper›PMID 37099633›Full record

ArticleScience translational medicine2023

Cloning a profibrotic stem cell variant in idiopathic pulmonary fibrosis.

Shan Wang, Wei Rao, Ashley Hoffman, Jennifer Lin, Justin Li, Tao Lin, Audrey-Ann Liew, Matthew Vincent, Tinne C J Mertens, Harry Karmouty-Quintana and 14 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
7.2field-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

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

22 citing papers in PubMed, 28 citations in OpenAlex.

  1. Autologous transplantation of P63Cell reports. Medicine · 2024
    Trial
  2. Article
  3. Progenitor Resilience and the Early Onset of Chronic Lung Diseases: NHLBI workshop report.American journal of respiratory cell and molecular biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Integrated single-cell TCR analysis across tissue identifies GZMKInternational journal of biological sciences · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Lung stem cells and respiratory epithelial chimerism in transplantation.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  19. Review
  20. Review
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

24 authors at 12 institutions in 1 country.

Shan WangStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.ORCID 0000-0002-9035-2290
Wei RaoStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.ORCID 0000-0002-2975-7045
Ashley HoffmanStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.ORCID 0000-0001-7276-7532
Jennifer LinStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.ORCID 0000-0003-1460-0624
Justin LiAccuraScience, Johnston, IA 50131, USA.ORCID 0000-0001-9177-2759
Tao LinStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.
Audrey-Ann LiewStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.
Matthew VincentNuwa Medical Systems, Houston, TX 77479, USA.ORCID 0000-0003-4246-1078
Tinne C J MertensDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Harry Karmouty-QuintanaDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.ORCID 0000-0003-4753-9823
Christopher P CrumDepartment of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02215, USA.ORCID 0000-0001-7746-1436
Mark L MeterskyDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Connecticut School of Medicine, Farmington, CT 06032, USA.ORCID 0000-0003-1968-1400
David A SchwartzDepartments of Medicine and Microbiology and Immunology, University of Colorado School of Medicine, Aurora, CO 80045, USA.ORCID 0000-0001-6743-8443
Peter J A DaviesTexas A&M Health Institute of Biotechnology, Houston, TX 77030, USA.ORCID 0000-0003-0770-2796
Clifford StephanTexas A&M Health Institute of Biotechnology, Houston, TX 77030, USA.ORCID 0000-0003-0657-6484
Soma S K JyothulaLung Transplant Center at Memorial Hermann-Texas Medical Center, Houston, TX 77030, USA.ORCID 0000-0002-8837-7878
Ajay SheshadriDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-8091-0180
Erik Eddie SuarezDepartment of Medicine, Houston Methodist Hospital, Houston, TX 77030, USA.
Howard J HuangDepartment of Medicine, Houston Methodist Hospital, Houston, TX 77030, USA.ORCID 0000-0002-3358-6795
John F EngelhardtDepartment of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.ORCID 0000-0003-2389-9277
Burton F DickeyDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4780-1847
Kalpaj R ParekhDepartment of Surgery, Division of Cardiothoracic Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Frank D McKeonStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.ORCID 0000-0002-7747-9983
Wa XianStem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA.
University of Houston · USMethodist Hospital · USTexas A&M Health Science Center · USThe University of Texas Health Science Center at Houston · USThe University of Texas MD Anderson Cancer Center · USUniversity of Iowa · USBrigham and Women's Hospital · USJohnston Community College · USMemorial Hermann–Texas Medical Center · USTexas Medical Center · USUniversity of Colorado Denver · USUniversity of Connecticut · US

Funding

Vector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Amy Leanne Ryan · 1998 to 2026
$30.5M
Targeting early events in MUC5B-driven lung injury and fibrosisP01HL162607 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI David Albert Schwartz · 2023 to 2026
$12.4M
Common Stem Cell of Origin for Junctional and Gastric AdenocarcinomaR01CA272906 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Jaffer A. Ajani, FRANK D. MCKEON · 2022 to 2026
$4.6M
Pathogenesis of Airway Stem Cell Abnormalities in Obliterative BronchiolitisR01HL136370 · NHLBI · UNIVERSITY OF IOWA · PI Kalpaj Rajnikant Parekh, Wa Xian · 2019 to 2026
$4.2M
Controlling the core airway mucin secretion machinery to prevent pathophysiologyR01HL129795 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DICKEY, BURTON F · 2015 to 2023
$3.8M
MODELS OF SUBMUCOSAL GLAND DEVELOPMENT AND FUNCTIONR01DK047967 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI ENGELHARDT, JOHN F · 1993 to 2020
$3.8M
Biology of Submucosal Gland Stem Cells in the AirwayR01HL165404 · NHLBI · UNIVERSITY OF IOWA · PI ENGELHARDT, JOHN F · 2022 to 2025
$2.9M
Sineoculis Homeobox Homolog 1 (Six1) in Pulmonary FibrosisR01HL157100 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARMOUTY-QUINTANA, HARRY · 2021 to 2025
$2.8M
Pro-Inflammatory Stem Cell Variants in Cystic FibrosisR01HL149678 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MCKEON, FRANK D. · 2022 to 2025
$2.7M
Pathogenic Heterogeneity in Mucosal Stem Cells in Pediatric Crohn's DiseaseR01DK115445 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI XIAN, WA · 2018 to 2021
$2.6M
3'UTR Shortening In Pulmonary Vascular DiseaseR01HL138510 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARMOUTY-QUINTANA, HARRY · 2017 to 2021
$2.3M
Clonal Reconstruction and Targeting of the Correa SequenceR01CA241600 · NCI · UNIVERSITY OF HOUSTON · PI MCKEON, FRANK D. · 2019 to 2023
$2.3M
BLRD VA I01 BX005295Cancer Research UKNCI NIH HHS R01 CA241600NCI NIH HHS R01 CA272906NCI NIH HHS U24 CA228550NHLBI NIH HHS P01 HL162607NHLBI NIH HHS R01 HL129795NHLBI NIH HHS R01 HL136370NHLBI NIH HHS R01 HL138510NHLBI NIH HHS R01 HL149678NHLBI NIH HHS R01 HL157100NHLBI NIH HHS R01 HL165404NIDDK NIH HHS P30 DK054759NIDDK NIH HHS R01 DK047967NIDDK NIH HHS R01 DK115445
6 · The paper itself

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of lung alveoli with dense fibrotic matrices. Although the mechanisms initiating IPF remain unclear, rare and common alleles of genes expressed in lung epithelia, combined with aging, contribute to the risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified lung basal cell heterogeneity in IPF that might be pathogenic. We used single-cell cloning technologies to generate "libraries" of basal stem cells from the distal lungs of 16 patients with IPF and 10 controls. We identified a major stem cell variant that was distinguished from normal stem cells by its ability to transform normal lung fibroblasts into pathogenic myofibroblasts in vitro and to activate and recruit myofibroblasts in clonal xenografts. This profibrotic stem cell variant, which was shown to preexist in low quantities in normal and even fetal lungs, expressed a broad network of genes implicated in organ fibrosis and showed overlap in gene expression with abnormal epithelial signatures identified in previously published scRNA-seq studies of IPF. Drug screens highlighted specific vulnerabilities of this profibrotic variant to inhibitors of epidermal growth factor and mammalian target of rapamycin signaling as prospective therapeutic targets. This profibrotic stem cell variant in IPF was distinct from recently identified profibrotic stem cell variants in chronic obstructive pulmonary disease and may extend the notion that inappropriate accrual of minor and preexisting stem cell variants contributes to chronic lung conditions.

Indexed as

Idiopathic Pulmonary FibrosisCloning, MolecularFibroblastsHumansLungMyofibroblastsStem Cells

Identifiers

PMID37099633
PMCPMC10794039
OpenAlexW4367042152

What OpenQuestion holds

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Registered trials

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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.