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

• Published in: Cell genomics Vol. 4; no. 12; p. 100703
• Main Authors: Yuan, Jiamiao, Dong, Kangning, Wu, Haixu, Zeng, Xuerui, Liu, Xingyan, Liu, Yan, Dai, Jiapei, Yin, Jichao, Chen, Yongjie, Guo, Yongbo, Luo, Wenhao, Liu, Na, Sun, Yan, Zhang, Shihua, Su, Bing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.12.2024; Elsevier
• Subjects: Animals; anterior cingulate cortex; Biological Evolution; brain development; Cell Nucleus - metabolism; Chromatin - genetics; Chromatin - metabolism; cis-regulatory element; evolution; Evolution, Molecular; Genetics; Gyrus Cinguli - cytology; Gyrus Cinguli - metabolism; human accelerated regions; Humans; Macaca; Mice; multi-omics; Multiomics; Neurons - metabolism; Primates - genetics; single cell; Single-Cell Analysis; single-nucleotide changes; transcription factor; von Economo neuron; brain development; transcription factor; single cell; von Economo neuron; cis-regulatory element; multi-omics; single-nucleotide changes; evolution; anterior cingulate cortex; human accelerated regions
• ISSN: 2666-979X; 2666-979X
• DOI: 10.1016/j.xgen.2024.100703

The anterior cingulate cortex (ACC) of the human brain is involved in higher-level cognitive functions such as emotion and self-awareness. We generated profiles of human and macaque ACC gene expression and chromatin accessibility at single-nucleus resolution. We characterized the conserved patterns of gene expression, chromatin accessibility, and transcription factor binding in different cell types. Combining the published mouse data, we discovered the molecular identities and cell-lineage origin of the primate von Economo neurons (VENs). Our in vitro and in vivo experiments identified a group of primate-shared and human-specific VEN marker genes, such as PCSK6, ADAMTSL3, and CDHR3, potentially contributing to VEN morphogenesis. We demonstrated that the human-specific sequence changes account for the cellular and functional innovations in the ACC during primate evolution and human origin. These findings provide new insights into understanding the cellular composition and molecular regulation of ACC and its evolutionary role in shaping human-owned higher cognitive skills. [Display omitted] •Cross-species single-nucleus multiome profiling of anterior cingulate cortex•Dissection of molecular identity and cell-lineage origin of the primate VENs•Human-specific VEN marker genes affect neuron morphogenesis during development•Human-specific sequence changes account for regulatory divergence during evolution Yuan et al. conducted cross-species single-nucleus analyses of transcription and chromatin accessibility of the anterior cingulate cortex (ACC). They discovered novel primate-shared and human-specific VEN marker genes acting on cell morphogenesis during brain development, and they delineated the genetic basis of cellular and functional innovations in the ACC during evolution.