ArticleThe Journal of pathology2019
Discordant roles for FGF ligands in lung branching morphogenesis between human and mouse.
Article in The Journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
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- FGF family in health and disease.Molecular biomedicine · 2026Review
- Fibroblast Growth Factors in Lung Development and Regeneration: Mechanisms and Therapeutic Potential.Cells · 2025Review
- Why some and not others? Understanding vascular phenotypes in genetic developmental lung diseases.Current opinion in pediatrics · 2025Review
- Morphological and molecular aspects of lung development.Histology and histopathology · 2025Review
- Reinitiating lung development: a novel approach in the management of bronchopulmonary dysplasia.Respiratory research · 2024Review
- Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair.Genes & diseases · 2024Article
- Fetal hypoplastic lungs have multilineage inflammation that is reversed by amniotic fluid stem cell extracellular vesicle treatment.Science advances · 2024Article
- The Role of Biophysical Factors in Organ Development: Insights from Current Organoid Models.Bioengineering (Basel, Switzerland) · 2024Review
- NLRP3 inflammasome mediates abnormal epithelial regeneration and distal lung remodeling in silica‑induced lung fibrosis.International journal of molecular medicine · 2024Article
- Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.Genes · 2024Article
- Congenital lung malformations.Nature reviews. Disease primers · 2023Review
- The lung mesenchyme in development, regeneration, and fibrosis.The Journal of clinical investigation · 2023Review
- RTK signalling promotes epithelial columnar cell shape and apical junction maintenance in human lung progenitor cells.Development (Cambridge, England) · 2023Article
- FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Cancer-associated Mutations in Congenital Pulmonary Malformations: A Prospective Cohort.American journal of respiratory and critical care medicine · 2023Article
- A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.Nature cell biology · 2023Article
- Pulmonary endogenous progenitor stem cell subpopulation: Physiology, pathogenesis, and progress.Journal of intensive medicine · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Fibroblast growth factor (FGF) signaling plays an important role in lung organogenesis. Over recent decades, FGF signaling in lung development has been extensively studied in animal models. However, little is known about the expression, localization, and functional roles of FGF ligands during human fetal lung development. Therefore, we aimed to determine the expression and function of several FGF ligands and receptors in human lung development. Using in situ hybridization (ISH) and RNA sequencing, we assessed their expression and distribution in native human fetal lung. Human fetal lung explants were treated with recombinant FGF7, FGF9, or FGF10 in air-liquid interface culture. Explants were analyzed grossly to observe differences in branching pattern as well as at the cellular and molecular level. ISH demonstrated that FGF7 is expressed in both the epithelium and mesenchyme; FGF9 is mainly localized in the distal epithelium, whereas FGF10 demonstrated diffuse expression throughout the parenchyma, with some expression in the smooth muscle cells (SMCs). FGFR2 expression was high in both proximal and distal epithelial cells as well as the SMCs. FGFR3 was expressed mostly in the epithelial cells, with lower expression in the mesenchyme, while FGFR4 was highly expressed throughout the mesenchyme and in the distal epithelium. Using recombinant FGFs, we demonstrated that FGF7 and FGF9 had similar effects on human fetal lung as on mouse fetal lung; however, FGF10 caused the human explants to expand and form cysts as opposed to inducing epithelial branching as seen in the mouse. In conjunction with decreased branching, treatment with recombinant FGF7, FGF9, and FGF10 also resulted in decreased double-positive SOX2/SOX9 progenitor cells, which are exclusively present in the distal epithelial tips in early human fetal lung. Although FGF ligand localization may be somewhat comparable between developing mouse and human lungs, their functional roles may differ substantially. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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