ArticleCell stem cell2024
Generation of human alveolar epithelial type I cells from pluripotent stem cells.
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Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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72citing papers in PubMed
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72 citing papers in PubMed, 69 citations in OpenAlex.
- A 4D GelMA-Cad/Gelatin Hydrogel for High-Resolution DMD Bioprinting of Vascularized Soft Tissue Models.bioRxiv : the preprint server for biology · 2026Article
- Endowing Flexibility of Alveolar Type II Cells to Recapitulate Development From Lung Bud to Alveoli.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sustained YAP/TAZ activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling.JCI insight · 2026Article
- Co-optation of the regenerative role of type 2 alveolar cells in distal lung repair in mice by terminal airway epithelial cells in humans.bioRxiv : the preprint server for biology · 2026Article
- Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.Nature communications · 2026Article
- A comprehensive long RNA landscape of multi-regional porcine lung-derived small extracellular vesicles.BMC genomics · 2026Article
- Defective alveolar regeneration in emphysema: identifying dysfunctional cellular crosstalk and novel therapeutic opportunities for tissue repair.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Epigenetic de-repression of basal cell metaplasia in aging AT2 cells is a risk factor for idiopathic pulmonary fibrosis (IPF).bioRxiv : the preprint server for biology · 2026Article
- Leveraging factors that control alveolar epithelial cell fate enables large-scale expansion for lung tissue engineering.The Journal of clinical investigation · 2026Article
- Robust generation of distal respiratory airway organoids by an engineered cuboid chip.Journal of nanobiotechnology · 2026Article
- Macrophages orchestrate antiviral defense and epithelial repair in a human iPSC-derived alveolar air-liquid interface.JCI insight · 2026Article
- Long isoforms of the COPD risk gene FAM13A orchestrate human lung epithelial development.American journal of respiratory cell and molecular biology · 2026Article
- Interferon-γ selectively promotes survival of alveolar progenitor cells in a human lung organoid model.The EMBO journal · 2026Article
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Standardized pipeline for establishing, expanding, and differentiating airway and alveolar organoids from human BAL fluid.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- TP53/TAU axis regulates microtubule bundling to control alveolar stem cell-mediated regeneration.The Journal of clinical investigation · 2026Article
- Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation.bioRxiv : the preprint server for biology · 2026Article
- Efficient CRISPR-Cas RNP-based gene targeting of human AT2 cells.American journal of respiratory cell and molecular biology · 2026Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 1 country.
Claire L BurgessCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian 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 Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Pushpinder S BawaCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Konstantinos-Dionysios AlysandratosCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Kasey MinakinCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Lauren J AyersCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Michael P MorleyPenn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Apoorva BabuPenn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Carlos Villacorta-MartinCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Maria YampolskayaDepartment of Physics, Boston University, Boston, MA 02215, USA.
Anne HindsThe Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Bibek R ThapaCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Feiya WangCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Adeline MatschulatThe Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Pankaj MehtaDepartment of Physics, Boston University, Boston, MA 02215, USA.
Edward E MorriseyPenn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Xaralabos VarelasCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
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 Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.
Boston University · USUniversity of Pennsylvania · US
Funding
Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3MTranslational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3MBIOLOGY OF THE LUNG--MULTIDISCIPLINARY PROGRAMT32HL007035 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton, JOSEPH P MIZGERD · 1985 to 2026
$24.3MPatient-specific iPSCs to model and treat the inception of pulmonary fibrosisP01HL170952 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Konstantinos Alysandratos · 2024 to 2026
$11.4MEditing 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
$7.5MGenetic Investigation of Covid 19 in Lung DiseaseR01HL164929 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MARK L KAHN, EDWARD E MORRISEY · 2022 to 2026
$4.7MDefining epithelial polarity cues that direct cell fateR01HL124392 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI VARELAS, XARALABOS · 2014 to 2024
$4.5MA National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4MMODELING EMERGENT BEHAVIORS IN SYSTEMS BIOLOGY: A BIOLOGICAL PHYSICS APPROACHR35GM119461 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI Pankaj Mehta · 2016 to 2026
$3.6MNATIONAL BIOREPOSITORY OF LUNG DISEASE-SPECIFIC HUMAN INDUCED PLURIPOTENT STEM CELLS:THE PURPOSE OF THIS RESOURCE IS TO BUILD AND SUPPORT A CRITICAL75N92020C00005 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI N/A, N/A · 2021 to 2024
$2.6MNCATS NIH HHS U01 TR001810NCATS NIH HHS UL1 TR001430NHLBI NIH HHS 75N92020C00005NHLBI NIH HHS F31 HL158193NHLBI NIH HHS K08 HL163494NHLBI NIH HHS P01 HL170952NHLBI NIH HHS R01 HL095993NHLBI NIH HHS R01 HL124392NHLBI NIH HHS R01 HL164929NHLBI NIH HHS T32 HL007035NHLBI NIH HHS U01 HL134745NHLBI NIH HHS U01 HL134766NHLBI NIH HHS U01 HL152976NIEHS NIH HHS P30 ES013508NIGMS NIH HHS R35 GM119461
Abstract
Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.
Indexed as
Alveolar Epithelial CellsCell DifferentiationInduced Pluripotent Stem CellsCells, CulturedHumansPluripotent Stem CellsSignal TransductionTranscriptomealveolar epithelial type I cellsdirected differentiationHippo signalingLATS inhibitionlunglung epithelial reporterpluripotent stem cells
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