Evidence map›Paper›PMID 28463226›Full record

ArticleThe Journal of clinical investigation2017

Prospective isolation of NKX2-1-expressing human lung progenitors derived from pluripotent stem cells.

Finn Hawkins, Philipp Kramer, Anjali Jacob, Ian Driver, Dylan C Thomas, Katherine B McCauley, Nicholas Skvir, Ana M Crane, Anita A Kurmann, Anthony N Hollenberg and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 1 pooled it
7.8field-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

153 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Long isoforms of the COPD risk gene FAM13A orchestrate human lung epithelial development.American journal of respiratory cell and molecular biology · 2026
    Article
  7. Review
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  16. The mechanical microenvironment and lung stem cell fate.Frontiers in cell and developmental biology · 2026
    Review
  17. Review
  18. Review
  19. Article
  20. Article

93 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

19 authors at 8 institutions in 1 country.

Finn HawkinsCenter for Regenerative Medicine, and.
Philipp KramerCenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Anjali JacobCenter for Regenerative Medicine, and.
Ian DriverDepartment of Anatomy, UCSF, San Francisco, California, USA.
Dylan C ThomasCenter for Regenerative Medicine, and.
Katherine B McCauleyCenter for Regenerative Medicine, and.
Nicholas SkvirCenter for Regenerative Medicine, and.
Ana M CraneCenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Anita A KurmannCenter for Regenerative Medicine, and.
Anthony N HollenbergDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Sinead NguyenCenter for Regenerative Medicine, and.
Brandon G WongDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, Massachusetts, USA.
Ahmad S KhalilDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, Massachusetts, USA.
Sarah Xl HuangCenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Susan GuttentagDepartment of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University, Nashville, Tennessee, USA.
Jason R RockDepartment of Anatomy, UCSF, San Francisco, California, USA.
John M ShannonDivision of Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Brian R DavisCenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Darrell N KottonCenter for Regenerative Medicine, and.
Boston University · USBrown Foundation · USCenter for Neuroscience and Regenerative Medicine · USBeth Israel Deaconess Medical Center · USUniversity of California, San Francisco · USCincinnati Children's Hospital Medical Center · USColumbia University Irving Medical Center · USMonroe Carell Jr. Children's Hospital · US

Funding

Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3M
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
Derivation of Transplantable Lung Epithelial Progenitors from iPS CellsR01HL095993 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton · 2009 to 2026
$7.5M
A National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4M
Thyroid Follicular Cell Signaling and Development in HumansR01DK105029 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI ANTHONY N HOLLENBERG, Darrell N. Kotton · 2016 to 2026
$3.7M
MOLECULAR SIGNALS FOR TRAFFICKING SURFACTANT PROTEIN BR01HL059959 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI GUTTENTAG, SUSAN H. · 1998 to 2011
$3.4M
Bioengineering of Transplantable Humanized Lungs from iPS CellsR01HL108678 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N., VACANTI, JOSEPH P · 2011 to 2014
$2.8M
A National Resource for Lung disease-specific iPS cellsR24HL123828 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N., MOSTOSLAVSKY, GUSTAVO · 2014 to 2018
$2.7M
Epigenenomic and transcriptomic networks in normal and defective lung developmentR01HL128172 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N. · 2015 to 2018
$2.2M
iPSC Modeling of the Role of NKX2-1 in Human Lung Development and DiseaseR01HL122442 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N. · 2014 to 2017
$1.6M
NCATS NIH HHS U01 TR001810NCATS NIH HHS UL1 TR001430NHLBI NIH HHS R01 HL059959NHLBI NIH HHS R01 HL095993NHLBI NIH HHS R01 HL108678NHLBI NIH HHS R01 HL122442NHLBI NIH HHS R01 HL128172NHLBI NIH HHS R24 HL123828NHLBI NIH HHS U01 HL134766NIDDK NIH HHS R01 DK105029
6 · The paper itself

Abstract

It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an inability to purify or track these progenitors for detailed characterization. Here we have engineered and developmentally differentiated NKX2-1GFP reporter pluripotent stem cells (PSCs) in vitro to generate and isolate human primordial lung progenitors that express NKX2-1 but are initially devoid of differentiated lung lineage markers. After sorting to purity, these primordial lung progenitors exhibited lung epithelial maturation. In the absence of mesenchymal coculture support, this NKX2-1+ population was able to generate epithelial-only spheroids in defined 3D cultures. Alternatively, when recombined with fetal mouse lung mesenchyme, the cells recapitulated epithelial-mesenchymal developing lung interactions. We imaged these progenitors in real time and performed time-series global transcriptomic profiling and single-cell RNA sequencing as they moved through the earliest moments of lung lineage specification. The profiles indicated that evolutionarily conserved, stage-dependent gene signatures of early lung development are expressed in primordial human lung progenitors and revealed a CD47hiCD26lo cell surface phenotype that allows their prospective isolation from untargeted, patient-specific PSCs for further in vitro differentiation and future applications in regenerative medicine.

Indexed as

AnimalsCell DifferentiationCells, CulturedCell SeparationFlow CytometryGene Expression Regulation, EnzymologicHumansInduced Pluripotent Stem CellsMiceNuclear ProteinsThyroid Nuclear Factor 1Transcription FactorsTranscriptomeNkx2-1 protein, mouseNuclear ProteinsThyroid Nuclear Factor 1Transcription Factors

Identifiers

PMID28463226
PMCPMC5451263
OpenAlexW2611660641

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.