小柯机器人

瑞典卡罗林斯卡学院Patrick F. Sullivan、Jens Hjerling-Leffler等研究人员合作，利用大脑细胞类型的遗传鉴定揭示了帕金森氏病产生的原因。该项研究成果于2020年4月27日在线发表在《自然—遗传学》上。

研究人员将全基因组关联研究结果与来自整个小鼠神经系统的单细胞转录组数据进行整合，从而系统地识别了大脑复杂性状背后的细胞类型。研究人员表明，精神疾病主要与投射的兴奋性和抑制性神经元有关。神经系统疾病与不同的细胞类型有关，这与其他证据相一致。

值得注意的是，帕金森氏病不仅与胆碱能和单胺能神经元（包括多巴胺能神经元）遗传相关，而且与肠道神经元和少突胶质细胞遗传相关。使用死后脑转录组数据，即使在疾病进展的最早阶段，研究人员也证实了这些细胞的改变。

这项研究为理解复杂脑部疾病的细胞基础提供了重要框架，并揭示了少突胶质细胞在帕金森氏病中的未知作用。

据悉，全基因组关联研究已经发现了数百个与复杂的脑部疾病相关的基因座，但目前尚不清楚这些基因座在哪种细胞类型中活跃。

附：英文原文

Title: Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Author: Julien Bryois, Nathan G. Skene, Thomas Folkmann Hansen, Lisette J. A. Kogelman, Hunna J. Watson, Zijing Liu, Leo Brueggeman, Gerome Breen, Cynthia M. Bulik, Ernest Arenas, Jens Hjerling-Leffler, Patrick F. Sullivan

Issue&Volume: 2020-04-27

Abstract: Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease.

DOI: 10.1038/s41588-020-0610-9

Source: https://www.nature.com/articles/s41588-020-0610-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex