Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons.

Nature Communications
R. D. HodgeEd S Lein

Abstract

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.

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Citations

Sep 22, 2020·Journal of Neuropathology and Experimental Neurology·Sarah Jacot-DescombesPatrick R Hof
Dec 30, 2020·ELife·Jeremy A MillerAmy Bernard
Apr 1, 2021·Neuron·Lucas T GraybuckBosiljka Tasic
Jun 3, 2021·The Journal of Comparative Neurology·Joanna JacobKelly Lambert
Aug 21, 2021·Annual Review of Cell and Developmental Biology·Maria Antonietta Tosches

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Methods Mentioned

BETA
snRNA-seq
fluorescence-activated cell sorting
scRNA-seq
mFISH
RNA-seq
PCR
Assay

Software Mentioned

Smart
UMAP
RNA
QC
seq
NIS
R
PClamp
GenomicRanges
FindVariableFeatures

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