Evidence map›Paper›PMID 35355013›Full record

ArticleNature2022

Human distal airways contain a multipotent secretory cell that can regenerate alveoli.

Maria C Basil, Fabian L Cardenas-Diaz, Jaymin J Kathiriya, Michael P Morley, Justine Carl, Alexis N Brumwell, Jeremy Katzen, Katherine J Slovik, Apoorva Babu, Su Zhou and 18 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed, 1 pooled it
43.8field-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

214 citing papers in PubMed, 1 synthesis or guideline pooled it, 300 citations in OpenAlex.

  1. Pooled it
  2. Autologous transplantation of P63Cell reports. Medicine · 2024
    Trial
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  4. Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
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  16. Article
  17. Article
  18. Clinical phenotypes in αERJ open research · 2026
    Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 1 country.

Maria C Basil *Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Fabian L Cardenas-Diaz *Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jaymin J KathiriyaDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1807-8570
Michael P MorleyDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Justine CarlDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alexis N BrumwellDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jeremy KatzenDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katherine J SlovikDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Apoorva BabuDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Su ZhouDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Madison M KrempDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katherine B McCauleyCenter for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8817-7120
Shanru LiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joseph D PlanerDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shah S HussainDepartment of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Xiaoming LiuDepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.ORCID http://orcid.org/0000-0002-3902-9105
Rebecca WindmuellerPenn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yun YingDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kathleen M StewartDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michelle OysterDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jason D ChristieDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joshua M DiamondDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John F EngelhardtDepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.ORCID http://orcid.org/0000-0003-2389-9277
Edward CantuPenn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Steven M RoweDepartment of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0001-9045-0133
Darrell N KottonCenter for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9604-8476
Harold A ChapmanDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-5280-5527
Edward E MorriseyDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. emorrise@pennmedicine.upenn.edu.
University of Pennsylvania · USPenn Center for AIDS Research · USUniversity of California, San Francisco · USBoston University · USUniversity of Alabama at Birmingham · USUniversity of Iowa · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
Vector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Amy Leanne Ryan · 1998 to 2026
$30.5M
UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Brian R. Davis · 2007 to 2026
$23.0M
Pathology CoreP01HL152960 · NHLBI · UNIVERSITY OF IOWA · PI ENGELHARDT, JOHN F · 2020 to 2024
$11.6M
TRAINING IN PULMONARY IMMUNOLOGYT32HL007586 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 1985 to 2025
$8.8M
Editing Alveolar Progenitor Cells for Correction of Monogenic DiseaseU01HL134745 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTON, DARRELL N., MORRISEY, EDWARD E · 2016 to 2022
$8.3M
Epithelial stem/progenitor cells as repair agents in diffuse alveolar damageU01HL134766 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAPMAN, HAROLD A, KOTTON, DARRELL N. · 2016 to 2022
$8.1M
Wnt signaling in the alveolar nicheR01HL087825 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2008 to 2021
$6.4M
Translational Program in CFTR-Related Airway DiseasesR35HL135816 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2017 to 2022
$6.3M
Program to promote lung regeneration and block fibrosisR35HL150767 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAPMAN, HAROLD A · 2020 to 2025
$5.8M
Molecular pathways controlling alveolar epithelial remodeling in development and regenerationR01HL132999 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2016 to 2023
$4.6M
Multi-modal characterization of three human lung niches at the single cell levelU01HL148857 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2019 to 2023
$4.4M
NHLBI NIH HHS F32 HL143931NHLBI NIH HHS K08 HL130586NHLBI NIH HHS K08 HL150226NHLBI NIH HHS K08 HL163398NHLBI NIH HHS K23 HL121406NHLBI NIH HHS K99 HL155785NHLBI NIH HHS P01 HL152960NHLBI NIH HHS R01 HL087825NHLBI NIH HHS R01 HL132999NHLBI NIH HHS R01 HL165404NHLBI NIH HHS R03 HL135227NHLBI NIH HHS R35 HL135816NHLBI NIH HHS R35 HL150767NHLBI NIH HHS T32 HL007586NHLBI NIH HHS U01 HL134745NHLBI NIH HHS U01 HL134766NHLBI NIH HHS U01 HL148857NHLBI NIH HHS U01 HL152978NIDDK NIH HHS P30 DK054759NIDDK NIH HHS P30 DK072482NIDDK NIH HHS R01 DK047967NIDDK NIH HHS R37 DK047967NIEHS NIH HHS P30 ES013508NIH HHS HL134745NIH HHS HL148857
6 · The paper itself

Abstract

The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.

Indexed as

BronchiolesFerretsMultipotent Stem CellsPulmonary AlveoliAnimalsCell LineageHumansLungMicePulmonary Disease, Chronic Obstructive

Identifiers

PMID35355013
PMCPMC9297319
OpenAlexW4221078835

What OpenQuestion 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 OpenQuestion graph.