The Transcriptional Logic of Mammalian Neuronal Diversity

Abstract

The mammalian nervous system is constructed of many cell types, but the principles 9 underlying this diversity are poorly understood. To assess brain-wide transcriptional diversity, we 10 sequenced the transcriptomes of the largest collection of genetically and anatomically identified 11 neuronal classes. Using improved expression metrics that distinguish information content from 12 signal-to-noise-ratio, we found that homeobox transcription factors contain the highest 13 information about cell types and have the lowest noise. Genes that contribute the most to 14 neuronal diversity tend to be long and enriched in factors specifically involved in neuronal function.

Brain Transcriptome Databases: A User's Guide

“…In the 2000s, genetic access to specific cells in the brain became possible with the availability of transgenic mice expressing a reporter gene (e.g., EGFP) in specific cell types by random genomic integration or promoter-driven gene expression (Feng et al, 2000;Gong et al, 2003). In a pioneering study, Sugino et al (2006) leveraged genetic access to specific cell types and FACS to isolate glutamatergic and GABAergic neurons in the cortex, hippocampus, amygdala, and thalamus. The resulting microarray data revealed the transcriptomic profiles of 12 distinct adult neuronal populations in the mouse brain.…”

“…The HB Atlas (Kang et al, 2011), which characterized a large collection of human brain tissue at high spatial and temporal resolution, enabled more precise gene coexpression studies. In one example illustrating the use of these data, Shim et al (2012) sought to identify the transcriptional regulators of the Fezf2 E4 enhancer. Coexpression analysis between FEZF2 and members of the SOX transcription factor family was undertaken, leading to the identification of SOX4 and SOX11 as candidate regulators.…”

The molecular logic of synaptic wiring at the single cell level

“…Homeodomain transcription factors (TFs) have long been known to play important roles in the specification and differentiation of neurons (Allen et al, 2020;Deneris & Hobert, 2014;Domsch et al, 2019;Reilly et al, 2020;Sugino et al, 2019;Urbach et al, 2006Urbach et al, , 2016Zeisel et al, 2018).…”