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.

中文翻译：

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比较单细胞多组学鉴定灵长类动物大脑发育过程中神经祖细胞的进化变化


了解驱动人类皮层发育特征的细胞和遗传机制仍然是一个挑战。我们在发育中的猕猴和小鼠前额叶皮层 （PFC） 中生成了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，尽管皮层细胞组成在物种之间总体上是保守的，但祖细胞在细胞特性上表现出显着的进化差异。具体来说，人类神经祖细胞在生长因子和细胞外基质 （ECM） 通路中表现出广泛的转录重连。人类特异性祖细胞标志物 ITGA2 在胎儿小鼠皮层中的表达增加了祖细胞增殖和上层神经元的比例。这些转录分歧主要是由远端调节元件中活性的改变驱动的。具有人类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和塑造灵长类动物大脑进化的推定基因调控机制。