黑质
电池类型
转录组
生物
帕金森病
神经元
基因表达谱
发病机制
神经科学
细胞
细胞生物学
神经退行性变
中脑
多巴胺能
基因表达
疾病
基因
多巴胺
病理
医学
遗传学
中枢神经系统
免疫学
作者
Qian Wang,Minghui Wang,Insup Choi,Lily Sarrafha,Matthew H. Liang,Lap Ho,Kurt Farrell,Kristin G. Beaumont,Robert Sebra,Claudia De Sanctis,John F. Crary,Tim Ahfeldt,Joel Blanchard,Drew Neavin,Joseph E. Powell,Davis Da,Xiaoyan Sun,Bin Zhang,Zhenyu Yue
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-01-12
卷期号:10 (2)
标识
DOI:10.1126/sciadv.adi8287
摘要
Parkinson’s disease (PD) is characterized pathologically by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Whether cell types beyond DA neurons in the SN show vulnerability in PD remains unclear. Through transcriptomic profiling of 315,867 high-quality single nuclei in the SN from individuals with and without PD, we identified cell clusters representing various neuron types, glia, endothelial cells, pericytes, fibroblasts, and T cells and investigated cell type–dependent alterations in gene expression in PD. Notably, a unique neuron cluster marked by the expression of RIT2 , a PD risk gene, also displayed vulnerability in PD. We validated RIT2 -enriched neurons in midbrain organoids and the mouse SN. Our results demonstrated distinct transcriptomic signatures of the RIT2 -enriched neurons in the human SN and implicated reduced RIT2 expression in the pathogenesis of PD. Our study sheds light on the diversity of cell types, including DA neurons, in the SN and the complexity of molecular and cellular changes associated with PD pathogenesis.
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