ArticleCell stem cell2016
Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.
Open access · bronzeAbstract read
In one paragraph
Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed, 1 pooled it
17.6field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
262 citing papers in PubMed, 1 synthesis or guideline pooled it, 403 citations in OpenAlex.
- Assessing the consistency of iPSC and animal models in cystic fibrosis modelling: A meta-analysis.PloS one · 2022Pooled it
- TRPV4-driven ATP release activates CFTR through ADORA2B and P2RY2 receptors in the airway epithelium.iScience · 2026Article
- Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features.International journal of molecular sciences · 2026Review
- SMAD4-BPIFA1 Axis Governs Airway Antiviral Defense in Myhre Syndrome.Biomolecules · 2026Article
- Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Concurrent jamming and mesenchymal-to-epithelial transitions during airway basal stem cell differentiation.iScience · 2026Article
- Leveraging factors that control alveolar epithelial cell fate enables large-scale expansion for lung tissue engineering.The Journal of clinical investigation · 2026Article
- Separation of Human P63Analytical chemistry · 2026Article
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- A serum-free culture medium for long-term expansion of human airway basal stem cells.Stem cell research & therapy · 2026Article
- Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Research Advances and Disease Modeling in Respiratory Organoids.Biomedicines · 2026Review
- Review
- Control of airway basal stem cell-mediated lung repair by TGF-β signaling.Science advances · 2026Article
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Article
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Single-cell analysis of human airway epithelium identifies cell-type-specific responses tomBio · 2025Article
- Organotypic Airway Models Derived from Primary Human Nasal Epithelial Cells.Current allergy and asthma reports · 2025Review
- Human induced pluripotent stem cells for in vitro modeling of impaired mucociliary clearance in cystic fibrosis lung disease.Stem cell research & therapy · 2025Article
202 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
21 authors at 7 institutions in 1 country.
Hongmei MouCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Division of Pediatric Pulmonary Medicine, Massachusetts General Hospital for Children, Boston, MA 02114, USA.
Vladimir VinarskyCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Purushothama Rao TataCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Karissa BrazauskasCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Division of Pediatric Pulmonary Medicine, Massachusetts General Hospital for Children, Boston, MA 02114, USA.
Soon H ChoiDepartment of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Adrianne K CrookeDepartment of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Bing ZhangDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA.
George M SolomonDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Brett TurnerDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Hermann BihlerCFFT Lab, Cystic Fibrosis Foundation Therapeutics, Lexington, MA 01730, USA.
Jan HarringtonCFFT Lab, Cystic Fibrosis Foundation Therapeutics, Lexington, MA 01730, USA.
Allen LapeyDivision of Pediatric Pulmonary Medicine, Massachusetts General Hospital for Children, Boston, MA 02114, USA.
Colleen ChannickDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Colleen KeyesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Adam FreundDepartments of Medicine and Biochemistry, Stanford University, Stanford, CA 94305, USA.
Steven ArtandiDepartments of Medicine and Biochemistry, Stanford University, Stanford, CA 94305, USA.
Martin MenseCFFT Lab, Cystic Fibrosis Foundation Therapeutics, Lexington, MA 01730, USA.
Steven RoweDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
John F EngelhardtDepartment of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Ya-Chieh HsuDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Jayaraj RajagopalCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Division of Pediatric Pulmonary Medicine, Massachusetts General Hospital for Children, Boston, MA 02114, USA; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Otology and Laryngology, Massachusetts Eye and Ear, Boston, MA 02114, USA. Electronic address: jrajagopal@partners.org.
Massachusetts General Hospital · USCystic Fibrosis Foundation · USHarvard Stem Cell Institute · USUniversity of Alabama at Birmingham · USUniversity of Iowa · USBoston Children's Hospital · USStanford University · US
Funding
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5MVector CoreP01HL051670 · NHLBI · UNIVERSITY OF IOWA · PI MCCRAY, PAUL B · 1993 to 2019
$36.5MVector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Amy Leanne Ryan · 1998 to 2026
$30.5MLeveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1MREVERSING CELLULAR IMMORTALITY IN CANCERR35CA197563 · NCI · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2015 to 2021
$6.4MIntercellular communication and cell regulation in airway epithelial ensembles in regeneration and diseaseR01HL118185 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI RAJAGOPAL, JAYARAJ · 2014 to 2021
$4.2MNational Ferret Resource and Research Center on Lung DiseaseR24HL123482 · NHLBI · UNIVERSITY OF IOWA · PI ENGELHARDT, JOHN F · 2014 to 2018
$3.8MBiology of submucosal gland stem cells in the airwayR37DK047967 · NIDDK · UNIVERSITY OF IOWA · PI ENGELHARDT, JOHN F · 2005 to 2014
$3.8MMODELS OF SUBMUCOSAL GLAND DEVELOPMENT AND FUNCTIONR01DK047967 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI ENGELHARDT, JOHN F · 1993 to 2020
$3.8MDefining the role of Hippo signaling in airway injury repair and remodelingR01HL116756 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI RAJAGOPAL, JAYARAJ · 2013 to 2017
$2.2MHarvard Stem Cell Institute Training Program for Pre- and Post-Doctoral FellowsT32HL087735 · NHLBI · HARVARD UNIVERSITY · PI SCADDEN, DAVID T · 2008 to 2012
$1.7MRe-establishment of directional mucociliary transport after epithelial injuryK08HL124298 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI VINARSKY, VLADIMIR · 2014 to 2018
$796kNCI NIH HHS R35 CA197563NCI NIH HHS T32 CA009302NHLBI NIH HHS K08 HL124298NHLBI NIH HHS K99 HL127181NHLBI NIH HHS P01 HL051670NHLBI NIH HHS R00 HL127181NHLBI NIH HHS R01 HL116756NHLBI NIH HHS R01 HL118185NHLBI NIH HHS R21 HL108055NHLBI NIH HHS R21 HL109786NHLBI NIH HHS R24 HL123482NHLBI NIH HHS T32 HL087735NIAMS NIH HHS R00 AR063127NIDDK NIH HHS P30 DK054759NIDDK NIH HHS R01 DK047967NIDDK NIH HHS R37 DK047967NIEHS NIH HHS P30 ES005605
Abstract
Functional modeling of many adult epithelia is limited by the difficulty in maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell populations. We find that TGFβ/BMP/SMAD pathway signaling is strongly activated in luminal and suprabasal cells of several epithelia, but suppressed in p63+ basal cells. In airway epithelium, SMAD signaling promotes differentiation, and its inhibition leads to stem cell hyperplasia. Using dual SMAD signaling inhibition in a feeder-free culture system, we have been able to expand airway basal stem cells from multiple species. Expanded cells can produce functional airway epithelium physiologically responsive to clinically relevant drugs, such as CFTR modulators. This approach is effective for the clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers and therefore may be broadly applicable for modeling of epithelia.
Indexed as
Signal TransductionAnimalsCell DifferentiationCell ProliferationCell Self RenewalCellular SenescenceCiliaEpithelial CellsEpitheliumHumansKeratinocytesLungMice, Inbred C57BLMucusSmad ProteinsTelomereSmad Proteinsdedifferentiationdifferentiationdual SMAD signaling inhibitionepithelial basal and stems cellsp63(+) basal cellsreplicative exhaustionsenescencestemnesstelomeresTGFβ/BMP4/SMAD signaling
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.