Zhang Chi, Xie Zihong, Wang Ningli
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University Beijing 100730, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University Guangzhou 510060, Guangdong, China.
Am J Transl Res. 2025 Apr 15;17(4):2562-2576. doi: 10.62347/ZEOR5569. eCollection 2025.
OBJECTIVES: To investigate gene expression dynamics in adult primate neocortex and elucidate the molecular basis of these capabilities. METHODS: Whole-cell transcriptome data from primary visual cortex (V1) of cynomolgus monkeys were analyzed, focusing on inhibitory neurons derived from the medial ganglionic eminence. Using RNA velocity and scVelo algorithms, we investigated subtle gene expression shifts, identified key driver genes, and conducted functional enrichment analysis. RESULTS: Our analysis revealed that somatostatin ()+ neurons are generated prior to parvalbumin ()+ neurons, with gene expression trajectories resembling those observed in developing animals. However, certain well-established + and + neurons, such as long-projecting + chondrolectin ()+ neurons and + unc-5 netrin receptor B ()+ neurons, do not share the same lineage, suggesting distinct regulatory programs. Furthermore, we identified a set of genes strongly correlated with these trajectories, including dihydropyrimidinase like 3 (), osteocrin (), smoothelin (), meis homeobox 2 (), chromodomain helicase DNA binding protein 3 (), and chromodomain helicase DNA binding protein 5 (). Functional enrichment analysis suggested that these genes are associated with neural plasticity and axon growth. CONCLUSIONS: This study provides novel insights into the gene expression dynamics of the primate neocortex. Genes involved in neuronal development and plasticity may underlie the advanced information-processing capabilities in primates.
目的:研究成年灵长类动物新皮质中的基因表达动态,并阐明这些能力的分子基础。 方法:分析了食蟹猴初级视皮层(V1)的全细胞转录组数据,重点关注源自内侧神经节隆起的抑制性神经元。使用RNA速度和scVelo算法,我们研究了细微的基因表达变化,确定了关键驱动基因,并进行了功能富集分析。 结果:我们的分析表明,生长抑素(SST)+神经元在小白蛋白(PV)+神经元之前产生,其基因表达轨迹与在发育中的动物中观察到的相似。然而,某些成熟的SST+和PV+神经元,如长投射SST+软骨凝集素(CHODL)+神经元和PV+unc-5神经纤毛蛋白受体B(UNC5B)+神经元,并不具有相同的谱系,这表明存在不同的调控程序。此外,我们确定了一组与这些轨迹密切相关的基因,包括二氢嘧啶酶样3(DPYSL3)、骨分泌素(OSTN)、平滑肌肌动蛋白(SMO)、Meis同源盒2(MEIS2)、染色质结构域解旋酶DNA结合蛋白3(CHD3)和染色质结构域解旋酶DNA结合蛋白5(CHD5)。功能富集分析表明,这些基因与神经可塑性和轴突生长相关。 结论:本研究为灵长类动物新皮质的基因表达动态提供了新的见解。参与神经元发育和可塑性的基因可能是灵长类动物先进信息处理能力的基础。
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