Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons
Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons
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DOI：
10.1038/s41467-020-14952-3
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发表时间：
2020-03-03
影响因子：
16.6
通讯作者：
Lein, Ed S.
中科院分区：
文献类型：
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作者：
Hodge, Rebecca D.;Miller, Jeremy A.;Lein, Ed S.
von Economo神经元（VEN）是局限于人额叶皮层和前扣带皮层的第5层的双极、纺锤形神经元，其似乎选择性地易受神经精神病和神经变性疾病的影响，尽管对其他VEN细胞表型知之甚少。额叶皮层5的单核RNA测序鉴定了转录组学定义的细胞簇，其包含VEN，但也包含叉细胞和锥体神经元的子集。这种细胞簇与注释良好的小鼠分类的跨物种比对显示出与投射到脑下靶点的端脑外（ET）兴奋性神经元的强烈同源性。这个簇也显示出很强的同源性，一个假定的ET簇在人类颞叶皮层，但具有惊人的特定区域签名。总之，这些结果表明，静脉内皮细胞是一个区域独特类型的ET神经元。此外，我们描述了第一个膜片钳记录的神经切除组织，显示出独特的内在膜特性相对于相邻的锥体神经元的VENs。
von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identifies a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.