The normal and fibrotic mouse lung classified by spatial proteomic analysis

Area of Science:

• * Cellular and Molecular Biology
• * Proteomics and Bioinformatics
• * Pathology and Disease Mechanisms

Background:

• * Single-cell classification is crucial for understanding tissue homeostasis and disease.
• * Lung fibrosis is a complex condition involving dynamic cellular changes.
• * Spatial proteomics offers a method to study cell populations within their native tissue context.

Purpose of the Study:

• * To apply in situ spatial proteomics to classify cells in healthy and fibrotic mouse lungs.
• * To quantitatively assess the progression of lung fibrosis over four weeks.
• * To investigate cell-specific variations in a multidrug transporter during fibrosis.

Main Methods:

• * Multiplex antibody staining was performed on routinely processed mouse lung tissue.
• * A validated panel of 24 antibodies was used for cell classification.
• * Quantitative measurements were employed to track cellular changes and transporter levels.

Main Results:

• * Normal lung constituents (alveolar type I and II, bronchial epithelia, endothelial, muscular, stromal, hematopoietic cells) were classified.
• * Lung fibrosis progression was monitored over a four-week period.
• * Alveolar type 2 cells showed an early decline, while stromal cells progressively increased.
• * Cell-specific quantitative variations of a multidrug transporter were observed.

Conclusions:

• * In situ spatial proteomics effectively classifies diverse cell types in the mouse lung.
• * The study quantitatively demonstrates the progression of lung fibrosis.
• * Early decline in alveolar type 2 cells and increased stromal cells are central to the fibrotic process.