Table_2_Cell–Cell Communication Alterations via Intercellular Signaling Pathways in Substantia Nigra of Parkinson’s Disease.XLSX

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（Parkinson’s disease, PD）是一种以黑质（substantia nigra, SN）内多巴胺能神经元（dopaminergic neuron, DaN）丢失为特征的神经退行性运动障碍。尽管已有大量研究聚焦于多巴胺能神经元内部的帕金森病细胞内机制，但鲜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间的发病机制。本研究旨在通过生物信息学方法，在系统层面探究涉及多巴胺能神经元的细胞间通信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（Gene Expression Omnibus, GEO）中获取了3个已在线发表的人类黑质单细胞/单细胞核转录组测序（single-cell/single-nucleus transcriptomic sequencing, sc/snRNA-seq）数据集（GSE126838、GSE140231及GSE157783），并使用最新的整合算法之一Harmony对其进行整合。随后，我们将最新的细胞间通信分析算法CellChat应用于该整合数据集。研究首先发现，与对照组样本相比，帕金森病样本的整体细胞通信总量有所降低，而整体通信强度则有所提升。随后我们聚焦于涉及多巴胺能神经元的细胞间通信，发现帕金森病中多巴胺能神经元与其他细胞类型通过特定信号通路的通信发生了选择性改变，涵盖生长因子、神经营养因子、趋化因子等多条信号通路。本研究的生物信息学分析表明，涉及多巴胺能神经元的细胞间通信改变可能是帕金森病发病机制中此前被低估的一个方面，且具备潜在的新型转化应用价值。