Comparative cellular analysis of motor cortex in human, marmoset and mouse

Area of Science:

• Neuroscience
• Genomics
• Comparative Biology

Background:

• The primary motor cortex (M1) is crucial for fine-motor control and is conserved in mammals.
• Understanding M1's cellular composition across species is key to deciphering conserved and specialized functions.

Purpose of the Study:

• To comprehensively profile and compare the cellular and molecular makeup of the primary motor cortex (M1) across humans, marmoset monkeys, and mice.
• To establish a cross-species consensus classification of M1 cell types and identify conserved and divergent features.

Main Methods:

• High-throughput transcriptomic and epigenomic profiling of over 450,000 single nuclei.
• Cross-species comparative analysis of gene expression, DNA methylation, and chromatin states.
• Patch-seq to characterize specific cell types, including corticospinal Betz cells.

Main Results:

• Demonstrated a broadly conserved cellular makeup of M1 across the three species, with similarities correlating with evolutionary distance.
• Generated a consensus classification of neuronal and non-neuronal cell types based on conserved molecular identities.
• Identified species-specific specializations in cell-type proportions, gene expression, and regulatory mechanisms, with few conserved marker genes.

Conclusions:

• The primary motor cortex exhibits both robust molecular conservation and significant species-specific adaptations in cell types.
• Identified key genes and regulatory pathways underlying conserved cell-type identities and specialized functions in M1.
• Provides a foundational resource for understanding M1 evolution and cell-type diversity across mammals.