A single-cell mass cytometry-based atlas of the developing mouse brain.

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Mammalian brain development involves complex molecular changes across cell lineages.
• Single-cell RNA sequencing (scRNA-seq) has characterized RNA abundance, but single-cell protein data remains largely uncharacterized.

Purpose of the Study:

• To characterize single-cell protein abundances in the developing mammalian brain.
• To identify distinct cell lineages and developmental trajectories using protein-level measurements.
• To compare protein versus RNA expression for a comprehensive understanding of cell states.

Main Methods:

• Mass cytometry was performed on whole mouse brains (embryonic day E11.5-E12.5) and specific brain regions (E13.5-postnatal day P4).
• A 40-antibody panel analyzed over 24 million cells across biological replicates.
• Data analysis identified molecularly distinct cell clusters and developmental pathways.

Main Results:

• Identified 85 molecularly distinct cell clusters across various developmental stages and brain regions.
• Confirmed canonical molecular pathways involved in neurogenesis and gliogenesis.
• Predicted two distinct trajectories for cortical oligodendrogenesis.
• Observed significant differences between protein and RNA expression, highlighting the value of protein-level data.

Conclusions:

• Mass cytometry is a valuable and scalable platform for single-cell profiling of brain tissues.
• Protein-level measurements provide crucial insights into functional cell states that complement RNA data.
• This study provides a foundational protein atlas for the developing mammalian brain.