Single-nucleus multi-omics analyses reveal cellular and molecular innovations in the anterior cingulate cortex during...

Area of Science:

• Neuroscience
• Evolutionary Biology
• Genomics

Background:

• The anterior cingulate cortex (ACC) is vital for complex cognitive functions like emotion and self-awareness.
• Understanding the cellular and molecular basis of ACC evolution is key to comprehending human cognitive uniqueness.

Purpose of the Study:

• To profile gene expression and chromatin accessibility in human and macaque ACC at single-nucleus resolution.
• To identify conserved and divergent molecular features across primate ACC cell types.
• To elucidate the cellular origins and molecular underpinnings of primate von Economo neurons (VENs).

Main Methods:

• Single-nucleus RNA sequencing and ATAC-sequencing of human and macaque ACC.
• Comparative analysis of gene expression, chromatin accessibility, and transcription factor binding patterns.
• Integration of mouse data to trace VEN cell-lineage.
• In vitro and in vivo experiments to validate VEN marker genes.

Main Results:

• Detailed cell-type-specific gene expression and chromatin accessibility maps of the primate ACC.
• Identification of conserved molecular patterns in ACC cell types across primates.
• Discovery of the molecular identity and cell-lineage origin of primate VENs.
• Identification of primate-shared and human-specific VEN marker genes (e.g., PCSK6, ADAMTSL3, CDHR3) potentially involved in VEN development.
• Evidence that human-specific sequence changes drive ACC cellular and functional innovations.

Conclusions:

• The study provides a high-resolution molecular atlas of the primate ACC.
• Key genes and evolutionary events shaping VENs and human cognition have been identified.
• Findings offer insights into the cellular and molecular basis of human cognitive evolution originating in the ACC.