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

Heterogeneity among somatosensory neurons is necessary for internal and external sensation. Precise patterns of gene transcription orchestrated through enhancer activation maintain heterogeneity. Thus, high-resolution cell type classification, chromatin accessibility and its relation to enhancer activation can explain the governing principles for sensory neuron heterogeneity. Here, we generated an integrated atlas from high-quality scRNA-seq datasets of the dorsal root ganglion, including over 44,000 neurons. MERSCOPE spatial transcriptomics confirmed cell types in situ, including previously unrecognized neuronal types, and a spatial zonation of both neurons and non-neuronal cells. We generated a cell type specific open chromatin atlas that revealed enhancer driven regulons and gene-regulatory networks. These were organized into co-regulated gene-programs that together defined sensory neuron diversity. Cell type complexity was found to be generated by layered co-regulated transcriptional modules representing shared functions across different scales of the neuronal type hierarchy with cell type specific contribution as the exception.