FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells

Area of Science:

• Developmental Biology
• Regenerative Medicine
• Pulmonology

Background:

• Fibroblast Growth Factor (FGF) signaling is crucial for lung organogenesis.
• FGF10 does not induce branching in human fetal lungs, unlike in mice.
• FGF18 is upregulated during human lung development, suggesting a role in branching.

Purpose of the Study:

• To investigate the role of FGF18 in human lung branching morphogenesis.
• To understand the cellular and molecular mechanisms underlying FGF18's function in human lung development.

Main Methods:

• Human fetal lung explants from the pseudoglandular stage were cultured.
• Explants were treated with recombinant human FGF18.
• Analyses included gross morphology, cellular proliferation, progenitor cell markers (SOX2/SOX9), and gene expression (SOX9, FN1, COL2A1).

Main Results:

• FGF18 treatment significantly promoted lung explant branching.
• Epithelial proliferation increased, and distal bud progenitor cells (SOX2/SOX9 positive) were maintained.
• Mesenchymal expression of SOX9, FN1, and COL2A1, important for chondrocyte differentiation, was upregulated.

Conclusions:

• FGF18 plays a key role in human lung branching morphogenesis.
• FGF18 promotes branching by enhancing epithelial proliferation and maintaining progenitor cells.
• FGF18 regulates mesenchymal progenitor cells, potentially explaining the deeper cartilaginous airways in humans compared to mice.