Differential expression analysis of the transcriptome for human basal ganglia from normal donors and Parkinson’s disease patients

ZU Gao-Yu; YOU Lin-Ya

doi:10.16098/j.issn.0529-1356.2024.04.015

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Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (4) : 482-492. DOI: 10.16098/j.issn.0529-1356.2024.04.015

Differential expression analysis of the transcriptome for human basal ganglia from normal donors and Parkinson’s disease patients

ZU Gao-yu¹LI Feng-jiao¹XIAN Wei-wei¹GUO Yang-yang¹ ZHAO Bai-cheng¹ LI Wen-sheng¹ YOU Lin-ya^1,2*

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Abstract

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.

Key words

Basal ganglia / Parkinson’s disease / High-throughput transcriptome sequencing / Differential expression analysis / Human

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ZU Gao-yu LI Feng-jiao XIAN Wei-wei GUO Yang-yang ZHAO Bai-cheng LI Wen-sheng YOU Lin-ya. Differential expression analysis of the transcriptome for human basal ganglia from normal donors and Parkinson’s disease patients[J]. Acta Anatomica Sinica. 2024, 55(4): 482-492 https://doi.org/10.16098/j.issn.0529-1356.2024.04.015

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