ArticleDevelopment (Cambridge, England)2019
Glycogen synthase kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture.
Article in Development (Cambridge, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Current strategies and opportunities to manufacture cells for modeling human lungs.Advanced drug delivery reviews · 2020Pooled it
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- Human iPSC-derived airway models enable comparative analysis of SARS-CoV-2 infection in healthy and COPD bronchial epithelium.iScience · 2026Article
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
- Human Pluripotent Stem Cell-Derived Alveolar Organoids for Gene-editing and Lung Adenocarcinomas Modeling.International journal of biological sciences · 2025Article
- The next frontier in lung development and regeneration research: harnessing iPSC models to illuminate notch signaling pathways.Frontiers in cell and developmental biology · 2025Review
- Defining signals that promote human alveolar type I differentiation.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model.International journal of molecular sciences · 2024Article
- Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity.Tuberculosis and respiratory diseases · 2024Article
- Airway basal cells from human-induced pluripotent stem cells: a new frontier in cystic fibrosis research.Frontiers in cell and developmental biology · 2024Article
- Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration.Nature communications · 2023Article
- Design and Realization of Lung Organoid Cultures for COVID-19 Applications.Bio-design and manufacturing · 2023Article
- A distal lung organoid model to study interstitial lung disease, viral infection and human lung development.Nature protocols · 2023Review
- Differentiation of human induced pluripotent stem cells into functional lung alveolar epithelial cells in 3D dynamic culture.Frontiers in bioengineering and biotechnology · 2023Article
- Multipotent Embryonic Lung Progenitors: Foundational Units of In Vitro and In Vivo Lung Organogenesis.Advances in experimental medicine and biology · 2023Article
- Stable iPSC-derived NKX2-1+ lung bud tip progenitor organoids give rise to airway and alveolar cell types.Development (Cambridge, England) · 2022Article
- Expandable Lung Epithelium Differentiated from Human Embryonic Stem Cells.Tissue engineering and regenerative medicine · 2022Article
- Organoids capture tissue-specific innate lymphoid cell development in mice and humans.Cell reports · 2022Article
- Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease.JCI insight · 2022Article
- Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Although strategies for directed differentiation of human pluripotent stem cells (hPSCs) into lung and airway have been established, terminal maturation of the cells remains a vexing problem. We show here that in collagen I 3D cultures in the absence of glycogen synthase kinase 3 (GSK3) inhibition, hPSC-derived lung progenitors (LPs) undergo multilineage maturation into proximal cells, type I alveolar epithelial cells and morphologically mature type II cells. Enhanced cell cycling, one of the signaling outputs of GSK3 inhibition, plays a role in the maturation-inhibiting effect of GSK3 inhibition. Using this model, we show NOTCH signaling induced a distal cell fate at the expense of a proximal and ciliated cell fate, whereas WNT signaling promoted a proximal club cell fate, thus implicating both signaling pathways in proximodistal specification in human lung development. These findings establish an approach to achieve multilineage maturation of lung and airway cells from hPSCs, demonstrate a pivotal role of GSK3 in the maturation of lung progenitors and provide novel insight into proximodistal specification during human lung development.
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Registered trials
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.