Disrupted myelination network in the cingulate cortex of Parkinson's disease

作者：Song Xie, Jiajun Yang, Shenghui Huang, Yuanlan Fan, Tao Xu, Jiangshuang He, Jiahao Guo, Xiang Ji, Zhibo Wang, Peijun Li, Jiang‐Fan Chen, Yi Zhang · 发表于：IET Systems Biology · 年份：2022 · DOI：10.1049/syb2.12043 · 被引用次数：26 · 研究领域：Nuclear Receptors and Signaling、RNA regulation and disease、Neurogenesis and neuroplasticity mechanisms

The cingulate cortex is part of the conserved limbic system, which is considered as a hub of emotional and cognitive control. Accumulating evidence suggested that involvement of the cingulate cortex is significant for cognitive impairment of Parkinson's disease (PD). However, mechanistic studies of the cingulate cortex in PD pathogenesis are limited. Here, transcriptomic and regulatory network analyses were conducted for the cingulate cortex in PD. Enrichment and clustering analyses showed that genes involved in regulation of membrane potential and glutamate receptor signalling pathway were upregulated. Importantly, myelin genes and the oligodendrocyte development pathways were markedly downregulated, indicating disrupted myelination in PD cingulate cortex. Cell-type-specific signatures revealed that myelinating oligodendrocytes were the major cell type damaged in the PD cingulate cortex. Furthermore, downregulation of myelination pathways in the cingulate cortex were shared and validated in another independent RNAseq cohort of dementia with Lewy bodies (DLB). In combination with ATACseq data, gene regulatory networks (GRNs) were further constructed for 32 transcription factors (TFs) and 466 target genes among differentially expressed genes (DEGs) using a tree-based machine learning algorithm. Several transcription factors, including Olig2, Sox8, Sox10, E2F1, and NKX6-2, were highlighted as key nodes in a sub-network, which control many overlapping downstream targets associat...