Liu Yuting, Luo Xin, Sun Yiming, Chen Kaimin, Hu Ting, You Benhui, Xu Jiahao, Zhang Fengyun, Cheng Qing, Meng Xiaoyu, Yan Tong, Li Xiang, Qi Xiaoxuan, He Xiechao, Guo Xuejiang, Li Cheng, Su Bing
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing 100871, China.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Yunnan Key Laboratory of Integrative Anthropology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, 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 650107, China.
Dev Cell. 2025 Feb 3;60(3):414-428.e8. doi: 10.1016/j.devcel.2024.10.005. Epub 2024 Oct 30.
Understanding the cellular and genetic mechanisms driving human-specific features of cortical development remains a challenge. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility in the developing macaque and mouse prefrontal cortex (PFC). Comparing with published human data, our findings demonstrate that although the cortex cellular composition is overall conserved across species, progenitor cells show significant evolutionary divergence in cellular properties. Specifically, human neural progenitors exhibit extensive transcriptional rewiring in growth factor and extracellular matrix (ECM) pathways. Expression of the human-specific progenitor marker ITGA2 in the fetal mouse cortex increases the progenitor proliferation and the proportion of upper-layer neurons. These transcriptional divergences are primarily driven by altered activity in the distal regulatory elements. The chromatin regions with human-gained accessibility are enriched with human-specific sequence changes and polymorphisms linked to intelligence and neuropsychiatric disorders. Our results identify evolutionary changes in neural progenitors and putative gene regulatory mechanisms shaping primate brain evolution.
了解驱动人类皮质发育特定特征的细胞和遗传机制仍然是一项挑战。我们生成了发育中的猕猴和小鼠前额叶皮质（PFC）的转录组和染色质可及性的细胞类型解析图谱。与已发表的人类数据相比，我们的研究结果表明，尽管皮质细胞组成在物种间总体上是保守的，但祖细胞在细胞特性上表现出显著的进化差异。具体而言，人类神经祖细胞在生长因子和细胞外基质（ECM）途径中表现出广泛的转录重排。人类特异性祖细胞标志物ITGA2在胎鼠皮质中的表达增加了祖细胞增殖和上层神经元的比例。这些转录差异主要由远端调控元件的活性改变驱动。具有人类获得性可及性的染色质区域富含与智力和神经精神疾病相关的人类特异性序列变化和多态性。我们的结果确定了神经祖细胞的进化变化以及塑造灵长类大脑进化的推定基因调控机制。
