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
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, P.R. China; Yunnan Key Laboratory of Integrative Anthropology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, China; National Key Laboratory of Genetic Evolution and Animal Model, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
School of Mathematics, Renmin University of China, Beijing 100872, China; NCMIS, CEMS, RCSDS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China; School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Genom. 2024 Dec 11;4(12):100703. doi: 10.1016/j.xgen.2024.100703. Epub 2024 Dec 3.
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.
人类大脑的前扣带回皮质（ACC）参与诸如情感和自我意识等高级认知功能。我们在单核分辨率下生成了人类和猕猴ACC基因表达及染色质可及性的图谱。我们对不同细胞类型中基因表达、染色质可及性和转录因子结合的保守模式进行了表征。结合已发表的小鼠数据，我们发现了灵长类冯·埃科诺莫神经元（VENs）的分子特征和细胞谱系起源。我们的体外和体内实验确定了一组灵长类共享和人类特有的VEN标记基因，如PCSK6、ADAMTSL3和CDHR3，它们可能有助于VEN的形态发生。我们证明，人类特有的序列变化解释了灵长类动物进化和人类起源过程中ACC的细胞和功能创新。这些发现为理解ACC的细胞组成和分子调控及其在塑造人类特有的高级认知技能中的进化作用提供了新的见解。
