ArticleCell stem cell2020
Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors.
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Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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95citing papers in PubMed, 1 pooled it
16.1field-weighted citation impact, top 1% of its field
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Current strategies and opportunities to manufacture cells for modeling human lungs.Advanced drug delivery reviews · 2020Pooled it
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- The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells.bioRxiv : the preprint server for biology · 2026Article
- In silico modeling of anterior foregut endoderm differentiation towards lung epithelial progenitors.NPJ systems biology and applications · 2026Article
- The mechanical microenvironment and lung stem cell fate.Frontiers in cell and developmental biology · 2026Review
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- A molecular circuit regulates fate plasticity in emerging and adult AT2 cells.Nature communications · 2025Article
- Successful Delivery of Small Non-Coding RNA Molecules into Human iPSC-Derived Lung Spheroids in 3D Culture Environment.Biomedicines · 2025Article
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
- Pulmonary Emphysema: Current Understanding of Disease Pathogenesis and Therapeutic Approaches.Biomedicines · 2025Review
- SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Evaluating the Use of iPSC-Derived Models in Understanding the Pathogenesis of Childhood Interstitial Lung Disease.Pediatric pulmonology · 2025Review
- Cloned airway basal progenitor cells to repair fibrotic lung through re-epithelialization.Nature communications · 2025Article
- Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.Stem cell reports · 2025Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 2 countries.
Killian HurleyCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland; Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
Jun DingComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Carlos Villacorta-MartinCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Michael J HerrigesCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Anjali JacobCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Marall VedaieCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Konstantinos D AlysandratosCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Yuliang L SunCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Chieh LinMachine Learning Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15217, USA.
Rhiannon B WerderCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Jessie HuangCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Andrew A WilsonCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Aditya MithalCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Gustavo MostoslavskyCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Irene OglesbyDepartment of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland; Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
Ignacio S CaballeroCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Susan H GuttentagDepartment of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University, Nashville, TN 37232, USA.
Farida AhangariPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 16520, USA.
Naftali KaminskiPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 16520, USA.
Alejo Rodriguez-FraticelliStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Fernando CamargoStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Boston, MA 02115, USA.
Ziv Bar-JosephComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Machine Learning Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15217, USA. Electronic address: zivbj@andrew.cmu.edu.
Darrell N KottonCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.
Boston Medical Center · USBoston University · USCarnegie Mellon University · USBeaumont Hospital · IEBoston Children's Hospital · USYale University · USVanderbilt University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MProject-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3MTranscriptional and epigenetic heterogeneity of stem/progenitor cellsP01HL131477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI DANIEL G TENEN · 2017 to 2026
$24.6MBIOLOGY OF THE LUNG--MULTIDISCIPLINARY PROGRAMT32HL007035 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton, JOSEPH P MIZGERD · 1985 to 2026
$24.3MThe LungMAP Data Coordination Center for Next Gen Systems Biology of RespirationU24HL148865 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Bruce J Aronow, Nathan G. Salomonis · 2019 to 2026
$12.4MEditing Alveolar Progenitor Cells for Correction of Monogenic DiseaseU01HL134745 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTON, DARRELL N., MORRISEY, EDWARD E · 2016 to 2022
$8.3MEpithelial 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
$8.1MDerivation of Transplantable Lung Epithelial Progenitors from iPS CellsR01HL095993 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton · 2009 to 2026
$7.5MA National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4MNRSA Training CoreTL1TR001410 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N. · 2015 to 2024
$4.3MComprehensive, Flexible and FAIR Tools for the HuBMAP HIVEOT2OD026682 · OD · CARNEGIE-MELLON UNIVERSITY · PI PATEN, BENEDICT, RUFFALO, MATTHEW · 2018 to 2021
$3.4MA National Resource for Lung disease-specific iPS cellsR24HL123828 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N., MOSTOSLAVSKY, GUSTAVO · 2014 to 2018
$2.7MNCATS NIH HHS TL1 TR001410NCATS NIH HHS U01 TR001810NCATS NIH HHS UL1 TR001430NCATS NIH HHS UL1 TR001863NHLBI NIH HHS F30 HL142169NHLBI NIH HHS F31 HL134274NHLBI NIH HHS K99 HL146983NHLBI NIH HHS P01 HL131477NHLBI NIH HHS R01 HL095993NHLBI NIH HHS R01 HL122442NHLBI NIH HHS R01 HL128172NHLBI NIH HHS R24 HL123828NHLBI NIH HHS T32 HL007035NHLBI NIH HHS U01 HL134745NHLBI NIH HHS U01 HL134766NHLBI NIH HHS U24 HL148865NIGMS NIH HHS R01 GM108807NIGMS NIH HHS R01 GM122096NIH HHS OT2 OD026682
Abstract
Alveolar epithelial type 2 cells (AEC2s) are the facultative progenitors responsible for maintaining lung alveoli throughout life but are difficult to isolate from patients. Here, we engineer AEC2s from human pluripotent stem cells (PSCs) in vitro and use time-series single-cell RNA sequencing with lentiviral barcoding to profile the kinetics of their differentiation in comparison to primary fetal and adult AEC2 benchmarks. We observe bifurcating cell-fate trajectories as primordial lung progenitors differentiate in vitro, with some progeny reaching their AEC2 fate target, while others diverge to alternative non-lung endodermal fates. We develop a Continuous State Hidden Markov model to identify the timing and type of signals, such as overexuberant Wnt responses, that induce some early multipotent NKX2-1
Indexed as
LungPluripotent Stem CellsAlveolar Epithelial CellsCell DifferentiationHumansPulmonary AlveoliAlveolar epithelial type 2 cellscell fatecellular plasticitydirected differentiationDNA barcodingheterogeneityhidden Markov modelinduced pluripotent stem cellslungprogenitorssingle cell RNA sequencing
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