目的  分析人基底神经节各核团的分子标志物以及不同核团间、不同性别、疾病相关的差异表达，探讨差异表达基因的生物学功能。 方法 针对来源于10具人尸脑45个基底神经节核团样本，按是否有神经疾病分为对照组和帕金森病组，对照组按性别分为女性和男性组，提取各样本RNA进行高通量转录组测序。生物信息学分析鉴定对照组各核团的分子标志物、不同核团间、不同性别以及帕金森病相关的差异表达基因，并对差异表达基因进行基因富集分析和功能注释。 结果 测序分析发现，top差异表达基因包含尾状核的DRD1、FOXG1、FAM183A；黑质的SLC6A3、EN1、SLC18A2、TH；苍白球的MEPE、FGF10；底丘脑的SLC17A6、PMCH、SHOX2等。其中，壳核top差异表达基因与尾状核存在部分重叠，如DRD1、FOXG1等。对照组不同核团间鉴定出大量差异表达基因，尾状核与苍白球间存在数量最多的差异表达基因(9321)，其次是壳核与苍白球间(6341)，尾状核与黑质间(6054)。黑质与底丘脑间存在数量最少的差异表达基因(44)。基因富集分析发现，尾状核与苍白球间下调基因显著富集在神经元髓鞘形成、细胞迁移调节等；壳核与苍白球上调基因富集在化学突触传递、膜电位调节、金属离子转运、神经递质转运等，而下调基因富集在神经元髓鞘形成、细胞黏附等；尾状核与黑质上调基因富集在化学突触传递、轴突传导等，而下调基因富集在神经元髓鞘形成等。另外，尾状核、壳核、黑质、苍白球和底丘脑分别鉴定到性别差异上调基因468、548、1402、333和341个，以及下调基因756、988、2532、444和1372个。基因富集分析发现，上调基因大多富集在免疫反应相关通路，下调基因富集在化学突触传递等。最后，尾状核、壳核、黑质、苍白球和底丘脑分别鉴定出帕金森病特异上调基因709、852、276、507和416个，以及下调基因830、2014、1218、836和1730个。基因富集分析发现，上调基因大多富集在凋亡信号调节，下调基因大多富集在化学突触传递、动作电位调节等。 结论 我们发现并分析了人基底神经节不同核团的分子标志物、核团间差异、性别差异和帕金森病的相关差异。

Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes (DEGs) among different nuclei, gender, and Parkinson’s disease (PD), followed by the biological function annotations of the DEGs. Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups, and the control group was further categorized into female and male groups. RNA from each sample was extracted for high-throughput transcriptome sequencing. Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group, nuclei-specific, gender-specific, and PD-specific DEGs, followed by gene enrichment analysis and functional annotation. Results Sequencing analysis revealed top DEGs such as DRD1, FOXG1, and FAM183A in the caudate; SLC6A3, EN1, SLC18A2, and TH in the substantia nigra; MEPE and FGF10 in the globus pallidus; and SLC17A6, PMCH, and SHOX2 in the subthalamic nucleus. In them, putamen showed some overlapping DEGs with caudate, such as DRD1 and FOXG1. A significant number of DEGs were identified among different nuclei in the control group, with the highest number between caudate and globus pallidus (9321), followed by putamen and globus pallidus (6341), caudate and substantia nigra (6054), and substantia nigra and subthalamic nucleus (44). Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration. Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential, while downregulated DEGs were enriched in myelination and cell adhesion. Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction, while downregulated DEGs were enriched in myelination of neurons. Totally 468, 548, 1402, 333, and 341 gender-specific upregulated DEGs and 756, 988, 2532, 444, and 1372 downregulated DEGs were identified in caudate, putamen, substantia nigra, globus pallidus, and subthalamus nucleus. Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission. At last, 709, 852, 276, 507, and 416 PD-specific upregulated DEGs and 830, 2014, 1218, 836, and 1730 downregulated DEGs were identified in caudate, putamen, substantia nigra, globus pallidus, and subthalamus nucleus. Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation. Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei, as well as DEGs among different nuclei, different gender, and between control and PD.