ArticleCell stem cell2021
Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration.
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Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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100citing papers in PubMed
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100 citing papers in PubMed, 149 citations in OpenAlex.
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- Effects of LATS1/2 kinases inhibition on lung epithelial cells in a regeneration model.Molecular and cellular biochemistry · 2026Article
- Fibroblasts as regulators of lung immunity, repair and fibrosis.Nature reviews. Immunology · 2026Review
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Idiopathic pulmonary fibrosis from a multiscale mechanobiology perspective: Mechanisms and future therapeutic prospects.iScience · 2026Review
- Advances in Internal Organogenesis: Differentiation and Morphogenesis of Human Ventral Cavity Organs.Stem cell reviews and reports · 2026Review
- TP53/TAU axis regulates microtubule bundling to control alveolar stem cell-mediated regeneration.The Journal of clinical investigation · 2026Article
- BRD4 promotes endodermal cell fate during mammalian lung development.JCI insight · 2026Article
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State.Nature communications · 2026Article
- Airway Goblet Metaplasia Resulting from YAP/TAZ Deletion Drives Pulmonary Inflammatory Responses.American journal of respiratory cell and molecular biology · 2026Article
- Desflurane post-conditioning inhibits HMGB1 nucleocytoplasmic translocation via the SIRT1/HMGB1 axis to attenuate hepatic ischemia-reperfusion-induced acute lung injury in young rats.Frontiers in pharmacology · 2026Article
- Dose-dependent activation of the Hippo pathway by Type I and Type III interferons suppresses tissue repair by human bronchial epithelial cells.PLoS biology · 2026Article
- Transcriptional coordination in multicellular lineage differentiation during lung organogenesis: deciphering the role of epithelial cells as a microenvironmental regulatory hub.Frontiers in cell and developmental biology · 2026Review
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- A novel alveoli-on-chip platform for modeling cyclic stretch in patient-derived alveolar epithelial cells cultured from organoids.Lab on a chip · 2025Article
- Local photocrosslinking of native tissue matrix regulates lung epithelial cell mechanosensing and function.Nature materials · 2025Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Ian J PenkalaDepartment of Biological Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Derek C LibertiPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joshua PankinDepartment of Pediatrics, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Aravind SivakumarDepartment of Pediatrics, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Madison M KrempPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sowmya JayachandranDepartment of Pediatrics, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Jeremy KatzenPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
John P LeachPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rebecca WindmuellerPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Katharine StolzDepartment of Pediatrics, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Michael P MorleyPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Apoorva BabuPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Su ZhouPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
David B FrankPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: frankd@email.chop.edu.
Edward E MorriseyPenn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: emorrise@pennmedicine.upenn.edu.
Penn Center for AIDS Research · USChildren's Hospital of Philadelphia · USUniversity of Pennsylvania · US
Funding
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3MEditing Alveolar Progenitor Cells for Correction of Monogenic DiseaseU01HL134745 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTON, DARRELL N., MORRISEY, EDWARD E · 2016 to 2022
$8.3MWnt signaling in the alveolar nicheR01HL087825 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2008 to 2021
$6.4MMolecular pathways controlling alveolar epithelial remodeling in development and regenerationR01HL132999 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2016 to 2023
$4.6MGraduate Training in Developmental BiologyT32HD083185 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael Granato, Foteini Mourkioti · 2015 to 2026
$4.0MEpigenic Regulation of Lung Progenitor Repair and RegenerationU01HL110942 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2012 to 2016
$3.4MDevelopmental pathways regulating adult lung quiescenceR01HL132349 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2016 to 2019
$2.3MTranscriptional Regulation of Lung Alveolar RegenerationR01HL152194 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MORRISEY, EDWARD E · 2021 to 2024
$2.3MUnderstanding how alveolar epithelial cell stress drives aberrant repair in interstitial lung diseaseK08HL150226 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KATZEN, JEREMY BINDER · 2020 to 2024
$840kWnt-mediated epithelial-endothelial crosstalk in the generation and regeneration of the lung alveolusK08HL140129 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI FRANK, DAVID BRIAN · 2018 to 2022
$797kTemporal and transcriptional control of alveolar epithelial type 1 cell fate and plasticity during developmentF31HL140785 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI PENKALA, IAN JAMES · 2018 to 2019
$90kNHLBI NIH HHS F31 HL140785NHLBI NIH HHS K08 HL140129NHLBI NIH HHS K08 HL150226NHLBI NIH HHS L40 HL129325NHLBI NIH HHS R01 HL087825NHLBI NIH HHS R01 HL132349NHLBI NIH HHS R01 HL132999NHLBI NIH HHS R01 HL152194NHLBI NIH HHS U01 HL110942NHLBI NIH HHS U01 HL134745NICHD NIH HHS T32 HD083185NIEHS NIH HHS P30 ES013508
Abstract
Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung.
Indexed as
Alveolar Epithelial CellsLungAnimalsHomeostasisMiceRespiratory MucosaSignal Transductionalveoluscellular plasticityHippolungregeneration
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