Spatial organization, chromatin accessibility and gene-regulatory programs defining mouse sensory neurons

Area of Science:

• Neuroscience
• Genomics
• Cell Biology

Background:

• Somatosensory neuron heterogeneity is crucial for sensation.
• Gene transcription patterns, driven by enhancers, maintain this diversity.
• Understanding cell types and chromatin accessibility is key to explaining sensory neuron heterogeneity.

Purpose of the Study:

• To create a high-resolution cell type classification of sensory neurons.
• To investigate the relationship between chromatin accessibility and enhancer activation.
• To elucidate the principles governing sensory neuron heterogeneity.

Main Methods:

• Integrated analysis of published scRNA-seq datasets and resequenced dorsal root ganglion data (>44,000 neurons).
• MERSCOPE spatial transcriptomics for in situ cell type confirmation and spatial organization analysis.
• Construction of a cell type-specific open chromatin atlas to identify enhancer-driven regulons and gene-regulatory networks.

Main Results:

• Identification of previously unrecognized neuronal types within the dorsal root ganglion.
• Discovery of spatial zonation patterns for both neuronal and non-neuronal cells.
• Characterization of enhancer-driven regulons and gene-regulatory networks defining sensory neuron diversity through co-regulated gene programs.

Conclusions:

• Sensory neuron diversity arises from layered, co-regulated transcriptional modules.
• These modules represent shared functions across the neuronal hierarchy.
• Cell type-specific contributions are the exception, not the rule, in generating complexity.