Subcellular Single Cell Sequencing: mRNA Diversity of Individual Glutamatergic and GABAergic Hippocampal Neurons and their Dendrites.

Neurons transport a variety of mRNAs to their dendritic and axonal compartments where they are locally translated. These processes are essential for the functional specialization of these cellular structures. To explore both the intercellular variability and intracellular dynamics of neuronal compartments we characterized the somatic and dendritic transcriptome of single neurons. We used Laser Capture Microdissection to isolate the dendrites and soma of individual neurons from primary hippocampal cultures, followed by scRNA-seq to profile the mRNA content of these compartments. In total, we sequence 276 dendrites and their respective somata, 227 somata without the dendrites, and 16 negative controls (LCM cuts of areas without cellular content). We observed less cell-type specific differences in the dendritic transcriptome than in the somatic transcriptome. However, the dendritic localization of a subset of mRNAs does vary in a cell-type specific manner. Furthermore, we observed that the relation between somatic and dendritic abundance varies according to gene and is strongly influenced by cellular function. This study provides a framework for the regulation of the dendritic transcriptome within and across individual neurons. Examination of somatic and dendritic transcriptome of single neurons