ArticleBMC biology2016
Mesodermal ALK5 controls lung myofibroblast versus lipofibroblast cell fate.
Article in BMC biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Hypomethylation-mediated upregulation of PHOX1 promotes gastric cancer progression via transactivation of NGFR.Cell death discovery · 2025Article
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- Impaired myofibroblast proliferation is a central feature of pathologic post-natal alveolar simplification.eLife · 2024Article
- Impaired Myofibroblast Proliferation is a Central Feature of Pathologic Post-Natal Alveolar Simplification.bioRxiv : the preprint server for biology · 2024Article
- Prenatal FGFR2 Signaling via PI3K/AKT Specifies the PDGFRAAmerican journal of respiratory cell and molecular biology · 2024Article
- Article
- Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- Alveologenesis: What Governs Secondary Septa Formation.International journal of molecular sciences · 2021Review
- Expression of serum response factor in the lung mesenchyme is essential for development of pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Understanding Human Lung Development through In Vitro Model Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Review
- Single-cell analysis reveals fibroblast heterogeneity and myofibroblasts in systemic sclerosis-associated interstitial lung disease.Annals of the rheumatic diseases · 2019Article
- The Tcf21 lineage constitutes the lung lipofibroblast population.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Building and Regenerating the Lung Cell by Cell.Physiological reviews · 2019Review
- Matrix biomechanics and dynamics in pulmonary fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- TGF-β Signaling in Lung Health and Disease.International journal of molecular sciences · 2018Review
- Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis.Cell reports · 2018Article
- TGF-β Family Signaling in Ductal Differentiation and Branching Morphogenesis.Cold Spring Harbor perspectives in biology · 2018Review
- Role of Fibroblast Growth Factor 10 in Mesenchymal Cell Differentiation During Lung Development and Disease.Frontiers in genetics · 2018Article
- Fra-2 negatively regulates postnatal alveolar septation by modulating myofibroblast function.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Transforming growth factor-β stimulates Smad1/5 signaling in pulmonary artery smooth muscle cells and fibroblasts of the newborn mouse through ALK1.American journal of physiology. Lung cellular and molecular physiology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundEpithelial-mesenchymal cross talk is centerpiece in the development of many branched organs, including the lungs. The embryonic lung mesoderm provides instructional information not only for lung architectural development, but also for patterning, commitment and differentiation of its many highly specialized cell types. The mesoderm also serves as a reservoir of progenitors for generation of differentiated mesenchymal cell types that include αSMA-expressing fibroblasts, lipofibroblasts, endothelial cells and others. Transforming Growth Factor β (TGFβ) is a key signaling pathway in epithelial-mesenchymal cross talk. Using a cre-loxP approach we have elucidated the role of the TGFβ type I receptor tyrosine kinase, ALK5, in epithelial-mesenchymal cross talk during lung morphogenesis.
resultsTargeted early inactivation of Alk5 in mesodermal progenitors caused abnormal development and maturation of the lung that included reduced physical size of the sub-mesothelial mesoderm, an established source of specific mesodermal progenitors. Abrogation of mesodermal ALK5-mediated signaling also inhibited differentiation of cell populations in the epithelial and endothelial lineages. Importantly, Alk5 mutant lungs contained a reduced number of αSMA(pos) cells and correspondingly increased lipofibroblasts. Elucidation of the underlying mechanisms revealed that through direct and indirect modulation of target signaling pathways and transcription factors, including PDGFRα, PPARγ, PRRX1, and ZFP423, ALK5-mediated TGFβ controls a process that regulates the commitment and differentiation of αSMA(pos) versus lipofibroblast cell populations during lung development.
conclusionALK5-mediated TGFβ signaling controls an early pathway that regulates the commitment and differentiation of αSMA(pos) versus LIF cell lineages during 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.