Transcriptomic Landscape of von Economo Neurons in Human Anterior Cingulate Cortex Revealed by Microdissected-Cell...

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.