Huang Maoxin, Xu Liang, Liu Jin, Huang Pei, Tan Yuyan, Chen Shengdi
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
Front Aging Neurosci. 2022 Feb 25;14:828457. doi: 10.3389/fnagi.2022.828457. eCollection 2022.
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized with dopaminergic neuron (DaN) loss within the substantia nigra (SN). Despite bulk studies focusing on intracellular mechanisms of PD inside DaNs, few studies have explored the pathogeneses outside DaNs, or between DaNs and other cells. Here, we set out to probe the implication of intercellular communication involving DaNs in the pathogeneses of PD at a systemic level with bioinformatics methods. We harvested three online published single-cell/single-nucleus transcriptomic sequencing (sc/snRNA-seq) datasets of human SN (GSE126838, GSE140231, and GSE157783) from the Gene Expression Omnibus (GEO) database, and integrated them with one of the latest integration algorithms called Harmony. We then applied CellChat, the latest cell-cell communication analytic algorithm, to our integrated dataset. We first found that the overall communication quantity was decreased while the overall communication strength was enhanced in PD sample compared with control sample. We then focused on the intercellular communication where DaNs are involved, and found that the communications between DaNs and other cell types via certain signaling pathways were selectively altered in PD, including some growth factors, neurotrophic factors, chemokines, etc. pathways. Our bioinformatics analysis showed that the alteration in intercellular communications involving DaNs might be a previously underestimated aspect of PD pathogeneses with novel translational potential.
帕金森病（PD）是一种神经退行性运动障碍，其特征是黑质（SN）内多巴胺能神经元（DaN）丧失。尽管大量研究聚焦于多巴胺能神经元内帕金森病的细胞内机制，但很少有研究探索多巴胺能神经元外或多巴胺能神经元与其他细胞之间的发病机制。在此，我们着手用生物信息学方法在系统水平上探究涉及多巴胺能神经元的细胞间通讯在帕金森病发病机制中的作用。我们从基因表达综合数据库（GEO）中获取了三个在线发表的人类黑质单细胞/单细胞核转录组测序（sc/snRNA-seq）数据集（GSE126838、GSE140231和GSE157783），并使用一种名为Harmony的最新整合算法将它们整合。然后，我们将最新的细胞间通讯分析算法CellChat应用于我们的整合数据集。我们首先发现，与对照样本相比，帕金森病样本中的总体通讯量减少而总体通讯强度增强。然后，我们聚焦于涉及多巴胺能神经元的细胞间通讯，发现多巴胺能神经元与其他细胞类型之间通过某些信号通路的通讯在帕金森病中发生了选择性改变，包括一些生长因子、神经营养因子、趋化因子等通路。我们的生物信息学分析表明，涉及多巴胺能神经元的细胞间通讯改变可能是帕金森病发病机制中一个此前被低估的方面，具有新的转化潜力。
