加拿大道格拉斯大学精神卫生研究所Gustavo Turecki研究组近日取得一项新成果。他们发现严重抑郁症（MDD）前额叶皮层的单核转录组学与少突胶质细胞前体细胞（OPC）和兴奋性神经元有关。相关论文发表在2020年4月27日出版的《自然-神经科学》杂志上。
他们使用单核转录组学研究了患有MDD（n = 17）的男性个体和健康对照组（n = 17）的背外侧前额叶皮层约80000个核。他们鉴定出26个细胞簇，其中超过60％的簇之间存在差异基因表达。他们发现最大的失调出现在深层兴奋性神经元和不成熟的OPC中，这些几乎占基因表达所有变化的一半（47％）。这些结果凸显了剖析特定细胞类型对该疾病的贡献的重要性，并为寻找新的研究途径和新的治疗靶标提供了机会。
据了解，MDD对全球疾病负担产生了巨大影响，影响了全球数百万人，在近三十年来一直是导致残疾的主要原因。过去的MDD分子研究使用了死后脑组织的大量匀浆，这掩盖了单个细胞类型内基因表达的变化。
附：英文原文
Title: Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons
Author: Corina Nagy, Malosree Maitra, Arnaud Tanti, Matthew Suderman, Jean-Francois Throux, Maria Antonietta Davoli, Kelly Perlman, Volodymyr Yerko, Yu Chang Wang, Shreejoy J. Tripathy, Paul Pavlidis, Naguib Mechawar, Jiannis Ragoussis, Gustavo Turecki
Issue&Volume: 2020-04-27
Abstract: Major depressive disorder (MDD) has an enormous impact on global disease burden, affecting millions of people worldwide and ranking as a leading cause of disability for almost three decades. Past molecular studies of MDD employed bulk homogenates of postmortem brain tissue, which obscures gene expression changes within individual cell types. Here we used single-nucleus transcriptomics to examine ~80,000 nuclei from the dorsolateral prefrontal cortex of male individuals with MDD (n=17) and of healthy controls (n=17). We identified 26 cellular clusters, and over 60% of these showed differential gene expression between groups. We found that the greatest dysregulation occurred in deep layer excitatory neurons and immature oligodendrocyte precursor cells (OPCs), and these contributed almost half (47%) of all changes in gene expression. These results highlight the importance of dissecting cell-type-specific contributions to the disease and offer opportunities to identify new avenues of research and novel targets for treatment.
DOI: 10.1038/s41593-020-0621-y
Source: https://www.nature.com/articles/s41593-020-0621-y
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
