ArticleLife science alliance2022
Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes.
Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- Endothelial Continuum and Capillary Specialization in Pulmonary Vascular Development.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Machine learning integrated extracellular vesicle proteome analysis for early markers of bronchopulmonary dysplasia.Function (Oxford, England) · 2026Article
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- 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
- VEGF-A isoforms induce the expression of APLN in endothelial cells during human prenatal lung development.Frontiers in cell and developmental biology · 2025Article
- Genomic structural variation contributes to evolved changes in gene expression in high-altitude Tibetan sheep.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Targeting the lung endothelial niche to promote angiogenesis and regeneration: A review of applications.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptation to breathing is a critical step in lung function and it is crucial for organismal survival. Alveoli are the lung gas exchange units and their development, from late embryonic to early postnatal stages, requires feedbacks between multiple cell types. However, how the crosstalk between the alveolar cell types is modulated to anticipate lung adaptation to breathing is still unclear. Here, we uncovered a synchronous alternative splicing switch in multiple genes in the developing mouse lungs at the transition to birth, and we identified hnRNP A1, Cpeb4, and Elavl2/HuB as putative splicing regulators of this transition. Notably, we found that <i>Vegfa</i> switches from the <i>Vegfa</i> 164 isoform to the longer <i>Vegfa</i> 188 isoform exclusively in lung alveolar epithelial AT1 cells. Functional analysis revealed that VEGFA 188 (and not VEGFA 164) drives the specification of Car4-positive aerocytes, a subtype of alveolar endothelial cells specialized in gas exchanges. Our results reveal that the cell type-specific regulation of <i>Vegfa</i> alternative splicing just before birth modulates the epithelial-endothelial crosstalk in the developing alveoli to promote lung adaptation to breathing.
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Registered trials
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