Cerebral cortical neuron diversity and development at single-cell resolution

Over a century of efforts to categorize the astonishing diversity of cortical neurons has relied on criteria of morphology, electrophysiology, ontology, and the expression of a few transcripts and proteins. The rapid development of single-cell RNA sequencing (scRNA-seq) adds genome-wide gene expression patterns to this list of criteria, and promises to reveal new insights into the transitions that establish neuronal identity during development, differentiation, activity, and disease. Comparing single neuron data to reference atlases constructed from hundreds of thousands of single-cell transcriptomes will be critical to understanding these transitions and the molecular mechanisms that drive them. We review early efforts, and discuss future challenges and opportunities, in applying scRNA-seq to the elucidation of neuronal subtypes and their development.