State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
Cereb Cortex. 2019 Feb 1;29(2):838-851. doi: 10.1093/cercor/bhy286.
The von Economo neurons (VENs) are specialized large bipolar projection neurons with restricted distribution in the human brain, and they are far more abundant in humans than in non-human primates. However, VEN functions remain elusive due to the difficulty of isolating VENs and dissecting their connections in the brain. Here, we combined laser-capture-microdissection with RNA sequencing to describe the transcriptomic profile of VENs from human anterior cingulate cortex (ACC). Using pyramidal neurons as reference cells, we identified 344 genes with VEN-associated expression differences, including 215 higher and 129 lower expression genes. Functional enrichment and protein-protein interaction network analyses showed that these genes with VEN-associated expression differences are involved in VEN morphogenesis and functions, such as dendrite branching and axon myelination, and many of them are associated with human social-emotional disorders. With the use of in situ hybridization and immunohistochemistry assays, we validated four novel VEN markers (VAT1L, CHST8, LYPD1, and SULF2). Collectively, we generated a full-spectrum expression profile of VENs from human ACC, greatly enlarging the pool of genes with VEN-associated expression differences that can help researchers to understand the role of VENs in normal and disordered human brains.
冯·埃科诺莫神经元（VENs）是一种特化的大型双极投射神经元，在人类大脑中的分布有限，其在人类中的丰富程度远高于非人类灵长类动物。然而，由于难以分离 VEN 并剖析其在大脑中的连接，因此 VEN 的功能仍然难以捉摸。在这里，我们结合激光捕获显微切割和 RNA 测序，描述了来自人类前扣带皮层（ACC）的 VEN 的转录组特征。我们使用锥体神经元作为参考细胞，鉴定出 344 个与 VEN 表达差异相关的基因，其中包括 215 个高表达基因和 129 个低表达基因。功能富集和蛋白质-蛋白质相互作用网络分析表明，这些与 VEN 表达差异相关的基因参与 VEN 的形态发生和功能，例如树突分支和轴突髓鞘形成，其中许多基因与人类社会情感障碍有关。通过原位杂交和免疫组织化学检测，我们验证了四个新的 VEN 标志物（VAT1L、CHST8、LYPD1 和 SULF2）。总的来说，我们从人类 ACC 生成了 VEN 的全谱表达谱，大大扩大了与 VEN 表达差异相关的基因库，这有助于研究人员了解 VEN 在正常和紊乱人类大脑中的作用。
