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PLoS Comput Biol. 2019 Jun 18;15(6):e1007113. doi: 10.1371/journal.pcbi.1007113. eCollection 2019 Jun.

Transcriptomic correlates of electrophysiological and morphological diversity within and across excitatory and inhibitory neuron classes.

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Department of Psychiatry, University of British Columbia, Vancouver BC, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver BC, Canada.
Michael Smith Laboratories, University of British Columbia, Vancouver BC, Canada.
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.


In order to further our understanding of how gene expression contributes to key functional properties of neurons, we combined publicly accessible gene expression, electrophysiology, and morphology measurements to identify cross-cell type correlations between these data modalities. Building on our previous work using a similar approach, we distinguished between correlations which were "class-driven," meaning those that could be explained by differences between excitatory and inhibitory cell classes, and those that reflected graded phenotypic differences within classes. Taking cell class identity into account increased the degree to which our results replicated in an independent dataset as well as their correspondence with known modes of ion channel function based on the literature. We also found a smaller set of genes whose relationships to electrophysiological or morphological properties appear to be specific to either excitatory or inhibitory cell types. Next, using data from PatchSeq experiments, allowing simultaneous single-cell characterization of gene expression and electrophysiology, we found that some of the gene-property correlations observed across cell types were further predictive of within-cell type heterogeneity. In summary, we have identified a number of relationships between gene expression, electrophysiology, and morphology that provide testable hypotheses for future studies.

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